BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t...BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.展开更多
BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associa...BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC.展开更多
Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1...Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1 ）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and matrix metalloproteinase-13 （ MMP-13 ） in lung tissue. Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone （25-800 mg · kg^-l · d^-1 ）, dexamethasone （3 mg/kg）, or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg · kg^-1 · d^-1 at 7 days or 14 daYs after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in luffg tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxypro- line. Expression of proteins of TGF-β1 TIMP-1, and MMP-13 were detected by Western blotting. Results At doses of 25, 50, and 100 mg· kg^- 1 · d ^- 1, pirfenidone had significant anti-fibrotic effects for bleomy- cin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg · kg^-1 ·d^ -1（ HE： P 〈 0. 01, P 〈 0.01, and P = 0.064; sirius red： P 〈0.05, P 〈 0.01, and P 〈 0.05 ; hydroxyproline： P = 0.595, P 〈 0.01, and P = 0.976）. Pirfenidone at a dosage of 50 mg · kg^- l · d^-1 inhibited protein expression of TGF-131 and TIMP-1 in lung tissue in the early phase （0.79 and 0.75 times of control group）, but had no effect on ex- nr^eelnn nf MMP-13. Conclusion Low dose pirfenidone, especially at dosage of 50 mg · kg^-1 · d^-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-131 and TIMP-β1 in lung tissue.展开更多
AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polym...AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.展开更多
AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of t...AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of this study was to evaluate the effect of ulcerative colitis(UC)on MMP- 1 and TIMP-1 plasma concentrations,as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1(13.7±0.2 ng/ml)and TIMP-1(799±140 ng/ml)were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively).There was no correlation between TIMP-1 and MMP-1 concentrations (r=0.02).TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration.There was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP- 1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.展开更多
AIM： To study the relationship between interleukin-lbeta （IL-1β） up-regulating tissue inhibitor of matrix metalloproteinase-1 （TIMMP-1） mRNA expression and phosphorylation of both c-jun N-terminal kinase （INK）...AIM： To study the relationship between interleukin-lbeta （IL-1β） up-regulating tissue inhibitor of matrix metalloproteinase-1 （TIMMP-1） mRNA expression and phosphorylation of both c-jun N-terminal kinase （INK） and p38 in rat heffatic stellate cells （HSC）. METHODS： RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC. RESULTS： TIMMP-1 mRNA expression （1.191± 0.079） was much higher after treatment with IL-1β （10 ng/mL） for 24 h than in control group （0.545±0.091） （P〈0.01）. IL-1β activated INK and p38 in a time-dependent manner. After stimulation with IL-1β for 0, 5, 15, 30, 60 and 120 min, the INK activity was 0.982±0.299, 1.501±0.720, 2.133±0.882, 3.360±0.452, 2.181±0.789, and 1.385 ± 0.368, respectively. There was a significant difference in JNK activity at 15 min （P〈 0.01）, 30 min （P〈 0.01） and 60 min （P〈0.01） in comparison to that at 0 min. The p38 activity was 1.061±0.310, 2.050±0.863, 2.380±0.573, 2.973±0.953, 2.421±0.793, and 1.755 ± 0.433 at the 6 time points （0, 5, 15, 30, 60 and 120 min） respectively. There was a significant difference in p38 activity at 5 min （P〈0.05）, 15 min （P〈0.01）, 30 min （P〈0.01） and 60 min （P〈0.01） compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups pretreated with different concentrations of SP600125 （10 μmol/L, 1.022±0.113; 20 μmol/L, 0.869±0.070; 40 μmol/L, 0.666±0.123）. Their decreases were all significant （P〈0.05, P〈0.01, P〈0.01） in comparison to control group （without SP600125 treatment, 1.163±0.107）. In the other 3 groups pretreated with different concentrations of SB203580 （10 μmol/L, 1.507±0.099; 20 μmol/L, 1.698±0.107; 40 μmol/L, 1.857±0.054）, the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group （without SB203580 treatment, 1.027 ± 0.061） with a significant statistical significance （P〈 0.01）. CONCLUSION： IL-1β has a direct action on hepatic fibrosis by up-regulating TIMMP-1 mRNA expression in ratessionin in rate HSC.JNK and p38 mitogen-activated protein kinases （MAPKs） are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and .INK pathways cooperatively mediate TIMP-1 mRNA expression in rat HSC.展开更多
Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and...Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. Matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.展开更多
AIM: To investigate the expression of matrix metallopr-oteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10). METHODS: Hepatic fibro...AIM: To investigate the expression of matrix metallopr-oteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10). METHODS: Hepatic fibrosis was induced by CCI4 administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8 rats), CCI4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type IV collagenase through portal vein catheter and the suspension was centrifuged by 11% Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h. RESULTS: Compared to group N in the 7th wk, MMP-2 and TIMP-1 mRNA increased in group C (P= 0.001/0.001) and group I (P= 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNA in group I was still lower than that in group C (P = 0.005), but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P= 0.001) while decreased in group I (P = 0.042) compared with that in the 7th wk. Same results were found by immunocytochemistry. CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.展开更多
AIM:To evaluate the levels of preoperative serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in gastric cancer.METHODS:One hundred gastric cancer patients who underwent gast...AIM:To evaluate the levels of preoperative serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in gastric cancer.METHODS:One hundred gastric cancer patients who underwent gastrectomy were enrolled in this study.The serum concentrations of MMP-1 and TIMP-1 in these patients and in fifty healthy controls were determined using an enzyme-linked immunosorbent assay.RESULTS:Higher serum MMP-1 and TIMP-1 levels were observed in patients than in controls (P < 0.001).Serum MMP-1 and TIMP-1 levels were positively associated with morphological appearance,tumor size,depth of wall invasion,lymph node metastasis,liver metastasis,perineural invasion,and pathological stage.They were not significantly associated with age,gender,tumor location,or histological type.CONCLUSION:Increased MMP-1 and TIMP-1 were associated with gastric cancer.Although these markers are not good markers for diagnosis,these markers show in advanced gastric cancer.展开更多
Tissue inhibitor of m etalloprotease-1(TIM P-1)is a tissue inhibitor o f matrix metalloproteinases(MMPs).It however exerts multiple effects on biological processes,such as cell growth,proliferation,differentiation and...Tissue inhibitor of m etalloprotease-1(TIM P-1)is a tissue inhibitor o f matrix metalloproteinases(MMPs).It however exerts multiple effects on biological processes,such as cell growth,proliferation,differentiation and apoptosis,in an MMP-independent manner.This study aimed to examine the role of TIMP-1 in adipogenesis of adipose-derived stem cells(ASCs)and the underlying mechanism.We knocked down the TIMP-1 gene in ASCs through lentiviral vectors encoding TIMP-1 small interfering RNA(siRNA),and then found that the knockdown of TIMP-1 in ASCs promoted the adipogenic differentiation of stem cells and inhibited the Wnt/β-catenin signaling pathway in ASCs.We also noted that mutant TIMP-1 without the inhibitory activity on MMPs promoted the activation of Wnt/β-catenin pathway as well as the recombinant wild type TIMP-1 did,which indicated that the effect of TIMP-1 on Wnt/β-catenin pathway was MMPindependent.Our study suggested that TIMP-1 negatively regulated the adipogenesis of ASCs via the Wnt/β-catenin signaling pathway in an MMP-independent manner.展开更多
Objective Tissue inhibitor of metalloproteinase-1 （TIMP-1） is a muhifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role o...Objective Tissue inhibitor of metalloproteinase-1 （TIMP-1） is a muhifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy （PMD）. Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy （DMD）, Becker muscular dystrophy （BMD） , congenital muscular dystrophy （CMD） by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP- 1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD.展开更多
目的 探讨急性肺栓塞(APE)患者血浆金属蛋白酶组织抑制因子-1(TIMP-1)、血管内皮生长因子(VEGF)及潜在转化生长因子结合蛋白2(LTBP-2)水平与危险分层和死亡的关系。方法 选取2022年1月~2024年1月海口市第三人民医院收治的APE患者110例...目的 探讨急性肺栓塞(APE)患者血浆金属蛋白酶组织抑制因子-1(TIMP-1)、血管内皮生长因子(VEGF)及潜在转化生长因子结合蛋白2(LTBP-2)水平与危险分层和死亡的关系。方法 选取2022年1月~2024年1月海口市第三人民医院收治的APE患者110例进行危险分层,分为低危组(n=28)、中危组(n=43)和高危组(n=39);根据APE患者发生死亡情况分为存活组(n=79)和死亡组(n=31)。采用酶联免疫吸附法(ELISA)测定血浆TIMP-1,VEGF及LTBP-2水平;应用多元Logistic回归分析影响APE患者死亡的危险因素,绘制ROC曲线分析血浆TIMP-1,VEGF及LTBP-2水平预测APE患者死亡的价值;采用Pearson相关分析血浆TIMP-1,VEGF及LTBP-2水平与APE患者临床指标的相关性。结果 死亡组心率、B型脑钠肽(BNP)、D-二聚体、TIMP-1(207.15±62.84pg/ml vs 152.48±41.62pg/ml),VEGF(726.35±190.46pg/ml vs 419.27±115.28pg/ml)及LTBP-2(29.17±6.38ng/ml vs 13.26±3.70ng/ml)水平均明显高于存活组,差异具有统计学意义(t=5.386~21.194,均P<0.05)。高危组和中危组血浆TIMP-1(204.15±60.17 pg/ml,178.18±51.30pg/ml vs 148.20±34.80pg/ml),VEGF(720.83±204.18pg/ml,580.16±158.37pg/ml vs 412.15±109.26pg/ml)及LTBP-2(28.40±6.41ng/ml,21.37±5.26ng/ml vs 12.84±3.12ng/ml)水平均明显高于低危组(t=8.417~19.850),且高危组高于中危组(t=7.964,9.381,11.470),差异具有统计学意义(均P<0.05)。多元Logistic回归分析显示,血浆BNP,D-二聚体,TIMP-1,VEGF及LTBP-2水平升高是影响APE患者死亡的危险因素(均P<0.05)。ROC曲线分析显示,TIMP-1,VEGF及LTBP-2三项联合预测APE患者死亡的AUC(95%CI)最大[0.938(0.881~0.997)],其准确度为88.2%。Pearson相关分析显示,APE患者血浆TIMP-1,VEGF及LTBP-2水平与BNP及D-二聚体均呈正相关(r=0.416~0.753,均P<0.05)。结论 血浆TIMP-1,VEGF及LTBP-2水平升高与APE高危和死亡有关,三项联合对APE患者死亡具有较好的预测价值。展开更多
BACKGROUND： Matrix metalloproteinase-9 （MMP-9） can degrade collagen IV （the main structural ingredient of basilar membrane）, and it also plays an important role in tumor vascularization, tumor cell progression, f...BACKGROUND： Matrix metalloproteinase-9 （MMP-9） can degrade collagen IV （the main structural ingredient of basilar membrane）, and it also plays an important role in tumor vascularization, tumor cell progression, formation of metastatic focus, etc. Tissue inhibitor of metalloproteinase-1 （T1MP-1） can bind with MMP-9 to form 1 ： 1 compound and inhibit its activity, and can negatively regulate the tumor progression and metastasis. OBJECTIVE： To analyze the relationship of MMP-9 and T1MP-1 expressions with the pathological grade, metastasis and prognosis of malignant peripheral nerve sheath tumor （MPNST）. DESIGN： An observational comparative experiment. SETTING： Heze Medical College. PARTICIPANTS： Fifty-eight surgical pathological samples, which were clearly diagnosed to be MPNST, were collected from the pathological laboratory archives in the Department of Pathology, Heze Municipal Hospital from January 1988 to December 2003. The MPNST pathological types were common tumor in 53 cases, malignant triton tumor in 2 cases, epithelial MPNST in 2 cases and MPNST with gland differentiation in 1 case. The pathological grade was grade 1 in 11 cases, grade 2 in 24 cases and grade 3 in 23 cases. Besides, the resected tumor samples of 20 patients with benign peripheral nerve tumor （10 cases of nerve sheath tumor and 10 cases of neurofibromatosis） and the normal peripheral nerves （by-products of some surgeries） of 5 patients were also collected. The samples were used with the approval of the patients. Rat-anti-human MMP-9, TIMP-1 monoclonal antibody and S-P kit were purchased from Fuzhou Maixin Biotechnology, Co.,Ltd. METHODS： The documented paraffin blocks were again prepared to sections of 5 lJ m. The expressions of MMP-9 and TIMP-1 in the samples were detected with mmunohistochemical S-P method. The relationships of the MPNST severity, recurrence, metastasis and survival rate with the expressions of MMP-9 and TIMP-1 were analyzed. MAIN OUTCOME MEASURES： Relationships of MMP-9 and TIMP-1 expressions with the MPNST severity and prognosis. RESULTS： ①Expressions of MMP-9 and TIMP-1 in three tissues： MMP-9 and TIMP-1 stainings were mainly observed in cytoplasm. Among the 58 MPNST patients, the MMP-9 expression was significantly higher than those in normal peripheral nerve and benign tumor （P 〈 0.05）, while the TIMP-1 expression in MPNST was lower than those in normal peripheral nerve and benign tumor （P 〈 0.05）. ②Relationship of MMP-9 and TIMP-1 expressions with the severity and prognosis of MPNST： The expressions of both proteins were observed in the four subtypes. The positive expression of MMP-9 in the MPNST patients of grades 2 - 3 was significantly higher than that in the MPNST patients of grade 1 （P 〈 0.05）, while the expression of MMP-9 was significantly lower than that in the MPNST patients of grade 1 （P 〈 0.05）. The metastatic rate was positively correlated with MMP-9 expression （r =1.696, P 〈 0.05）, but negatively correlated with TIMP-1 expression （r = - 2.125, P 〈 0.05）. CONCLUSION： MMP-9 and TIMP-1 are associated with MPNST pathological grades and metastasis, and can be used as the indicators for judging the severity and orognosis of MPNST.展开更多
In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cereb...In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.展开更多
文摘BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.
基金the Science-Technology Planning Project of Guangxi,No.Guike-AD19245174Guangxi Training Program for Medical High-level Academic Leaders,No.6 of Guiweikejiaofa[2020]-15+3 种基金Bose Talent Highland,No.2020-3-2Building Projects from the Key Laboratory of Molecular Pathology(Hepatobiliary Diseases)of Guangxi,No.Guiweikejiaofa[2020]-17the Key Laboratory of Tumor Molecular Pathology of Guangxi Colleges and Universities,No.Guijiaokeyan[2022]-10Clinical Key Specialty Building Project(For Pathology)of Guangxi,No.Guiweiyifa[2022]-21.
文摘BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC.
基金Supported by National Ministry of Education Doctor Foundation of China(20020023045)
文摘Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1 ）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and matrix metalloproteinase-13 （ MMP-13 ） in lung tissue. Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone （25-800 mg · kg^-l · d^-1 ）, dexamethasone （3 mg/kg）, or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg · kg^-1 · d^-1 at 7 days or 14 daYs after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in luffg tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxypro- line. Expression of proteins of TGF-β1 TIMP-1, and MMP-13 were detected by Western blotting. Results At doses of 25, 50, and 100 mg· kg^- 1 · d ^- 1, pirfenidone had significant anti-fibrotic effects for bleomy- cin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg · kg^-1 ·d^ -1（ HE： P 〈 0. 01, P 〈 0.01, and P = 0.064; sirius red： P 〈0.05, P 〈 0.01, and P 〈 0.05 ; hydroxyproline： P = 0.595, P 〈 0.01, and P = 0.976）. Pirfenidone at a dosage of 50 mg · kg^- l · d^-1 inhibited protein expression of TGF-131 and TIMP-1 in lung tissue in the early phase （0.79 and 0.75 times of control group）, but had no effect on ex- nr^eelnn nf MMP-13. Conclusion Low dose pirfenidone, especially at dosage of 50 mg · kg^-1 · d^-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-131 and TIMP-β1 in lung tissue.
文摘AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.
文摘AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of this study was to evaluate the effect of ulcerative colitis(UC)on MMP- 1 and TIMP-1 plasma concentrations,as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1(13.7±0.2 ng/ml)and TIMP-1(799±140 ng/ml)were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively).There was no correlation between TIMP-1 and MMP-1 concentrations (r=0.02).TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration.There was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP- 1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.
文摘AIM： To study the relationship between interleukin-lbeta （IL-1β） up-regulating tissue inhibitor of matrix metalloproteinase-1 （TIMMP-1） mRNA expression and phosphorylation of both c-jun N-terminal kinase （INK） and p38 in rat heffatic stellate cells （HSC）. METHODS： RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC. RESULTS： TIMMP-1 mRNA expression （1.191± 0.079） was much higher after treatment with IL-1β （10 ng/mL） for 24 h than in control group （0.545±0.091） （P〈0.01）. IL-1β activated INK and p38 in a time-dependent manner. After stimulation with IL-1β for 0, 5, 15, 30, 60 and 120 min, the INK activity was 0.982±0.299, 1.501±0.720, 2.133±0.882, 3.360±0.452, 2.181±0.789, and 1.385 ± 0.368, respectively. There was a significant difference in JNK activity at 15 min （P〈 0.01）, 30 min （P〈 0.01） and 60 min （P〈0.01） in comparison to that at 0 min. The p38 activity was 1.061±0.310, 2.050±0.863, 2.380±0.573, 2.973±0.953, 2.421±0.793, and 1.755 ± 0.433 at the 6 time points （0, 5, 15, 30, 60 and 120 min） respectively. There was a significant difference in p38 activity at 5 min （P〈0.05）, 15 min （P〈0.01）, 30 min （P〈0.01） and 60 min （P〈0.01） compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups pretreated with different concentrations of SP600125 （10 μmol/L, 1.022±0.113; 20 μmol/L, 0.869±0.070; 40 μmol/L, 0.666±0.123）. Their decreases were all significant （P〈0.05, P〈0.01, P〈0.01） in comparison to control group （without SP600125 treatment, 1.163±0.107）. In the other 3 groups pretreated with different concentrations of SB203580 （10 μmol/L, 1.507±0.099; 20 μmol/L, 1.698±0.107; 40 μmol/L, 1.857±0.054）, the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group （without SB203580 treatment, 1.027 ± 0.061） with a significant statistical significance （P〈 0.01）. CONCLUSION： IL-1β has a direct action on hepatic fibrosis by up-regulating TIMMP-1 mRNA expression in ratessionin in rate HSC.JNK and p38 mitogen-activated protein kinases （MAPKs） are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and .INK pathways cooperatively mediate TIMP-1 mRNA expression in rat HSC.
基金funded by the Natural Science Foundation of Shandong Province (Therapeutic effects and mechanisms of low-frequency ultrasound combined with urokinase thrombolysis in treatment of cerebral infarction in rats),No. 2009ZRB14007
文摘Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. Matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.
基金Supported by the Science and Technology Project of Fujian Educational Committee, No. JA04198
文摘AIM: To investigate the expression of matrix metallopr-oteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10). METHODS: Hepatic fibrosis was induced by CCI4 administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8 rats), CCI4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type IV collagenase through portal vein catheter and the suspension was centrifuged by 11% Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h. RESULTS: Compared to group N in the 7th wk, MMP-2 and TIMP-1 mRNA increased in group C (P= 0.001/0.001) and group I (P= 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNA in group I was still lower than that in group C (P = 0.005), but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P= 0.001) while decreased in group I (P = 0.042) compared with that in the 7th wk. Same results were found by immunocytochemistry. CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.
文摘AIM:To evaluate the levels of preoperative serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in gastric cancer.METHODS:One hundred gastric cancer patients who underwent gastrectomy were enrolled in this study.The serum concentrations of MMP-1 and TIMP-1 in these patients and in fifty healthy controls were determined using an enzyme-linked immunosorbent assay.RESULTS:Higher serum MMP-1 and TIMP-1 levels were observed in patients than in controls (P < 0.001).Serum MMP-1 and TIMP-1 levels were positively associated with morphological appearance,tumor size,depth of wall invasion,lymph node metastasis,liver metastasis,perineural invasion,and pathological stage.They were not significantly associated with age,gender,tumor location,or histological type.CONCLUSION:Increased MMP-1 and TIMP-1 were associated with gastric cancer.Although these markers are not good markers for diagnosis,these markers show in advanced gastric cancer.
文摘Tissue inhibitor of m etalloprotease-1(TIM P-1)is a tissue inhibitor o f matrix metalloproteinases(MMPs).It however exerts multiple effects on biological processes,such as cell growth,proliferation,differentiation and apoptosis,in an MMP-independent manner.This study aimed to examine the role of TIMP-1 in adipogenesis of adipose-derived stem cells(ASCs)and the underlying mechanism.We knocked down the TIMP-1 gene in ASCs through lentiviral vectors encoding TIMP-1 small interfering RNA(siRNA),and then found that the knockdown of TIMP-1 in ASCs promoted the adipogenic differentiation of stem cells and inhibited the Wnt/β-catenin signaling pathway in ASCs.We also noted that mutant TIMP-1 without the inhibitory activity on MMPs promoted the activation of Wnt/β-catenin pathway as well as the recombinant wild type TIMP-1 did,which indicated that the effect of TIMP-1 on Wnt/β-catenin pathway was MMPindependent.Our study suggested that TIMP-1 negatively regulated the adipogenesis of ASCs via the Wnt/β-catenin signaling pathway in an MMP-independent manner.
文摘Objective Tissue inhibitor of metalloproteinase-1 （TIMP-1） is a muhifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy （PMD）. Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy （DMD）, Becker muscular dystrophy （BMD） , congenital muscular dystrophy （CMD） by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP- 1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD.
文摘目的 探讨急性肺栓塞(APE)患者血浆金属蛋白酶组织抑制因子-1(TIMP-1)、血管内皮生长因子(VEGF)及潜在转化生长因子结合蛋白2(LTBP-2)水平与危险分层和死亡的关系。方法 选取2022年1月~2024年1月海口市第三人民医院收治的APE患者110例进行危险分层,分为低危组(n=28)、中危组(n=43)和高危组(n=39);根据APE患者发生死亡情况分为存活组(n=79)和死亡组(n=31)。采用酶联免疫吸附法(ELISA)测定血浆TIMP-1,VEGF及LTBP-2水平;应用多元Logistic回归分析影响APE患者死亡的危险因素,绘制ROC曲线分析血浆TIMP-1,VEGF及LTBP-2水平预测APE患者死亡的价值;采用Pearson相关分析血浆TIMP-1,VEGF及LTBP-2水平与APE患者临床指标的相关性。结果 死亡组心率、B型脑钠肽(BNP)、D-二聚体、TIMP-1(207.15±62.84pg/ml vs 152.48±41.62pg/ml),VEGF(726.35±190.46pg/ml vs 419.27±115.28pg/ml)及LTBP-2(29.17±6.38ng/ml vs 13.26±3.70ng/ml)水平均明显高于存活组,差异具有统计学意义(t=5.386~21.194,均P<0.05)。高危组和中危组血浆TIMP-1(204.15±60.17 pg/ml,178.18±51.30pg/ml vs 148.20±34.80pg/ml),VEGF(720.83±204.18pg/ml,580.16±158.37pg/ml vs 412.15±109.26pg/ml)及LTBP-2(28.40±6.41ng/ml,21.37±5.26ng/ml vs 12.84±3.12ng/ml)水平均明显高于低危组(t=8.417~19.850),且高危组高于中危组(t=7.964,9.381,11.470),差异具有统计学意义(均P<0.05)。多元Logistic回归分析显示,血浆BNP,D-二聚体,TIMP-1,VEGF及LTBP-2水平升高是影响APE患者死亡的危险因素(均P<0.05)。ROC曲线分析显示,TIMP-1,VEGF及LTBP-2三项联合预测APE患者死亡的AUC(95%CI)最大[0.938(0.881~0.997)],其准确度为88.2%。Pearson相关分析显示,APE患者血浆TIMP-1,VEGF及LTBP-2水平与BNP及D-二聚体均呈正相关(r=0.416~0.753,均P<0.05)。结论 血浆TIMP-1,VEGF及LTBP-2水平升高与APE高危和死亡有关,三项联合对APE患者死亡具有较好的预测价值。
文摘BACKGROUND： Matrix metalloproteinase-9 （MMP-9） can degrade collagen IV （the main structural ingredient of basilar membrane）, and it also plays an important role in tumor vascularization, tumor cell progression, formation of metastatic focus, etc. Tissue inhibitor of metalloproteinase-1 （T1MP-1） can bind with MMP-9 to form 1 ： 1 compound and inhibit its activity, and can negatively regulate the tumor progression and metastasis. OBJECTIVE： To analyze the relationship of MMP-9 and T1MP-1 expressions with the pathological grade, metastasis and prognosis of malignant peripheral nerve sheath tumor （MPNST）. DESIGN： An observational comparative experiment. SETTING： Heze Medical College. PARTICIPANTS： Fifty-eight surgical pathological samples, which were clearly diagnosed to be MPNST, were collected from the pathological laboratory archives in the Department of Pathology, Heze Municipal Hospital from January 1988 to December 2003. The MPNST pathological types were common tumor in 53 cases, malignant triton tumor in 2 cases, epithelial MPNST in 2 cases and MPNST with gland differentiation in 1 case. The pathological grade was grade 1 in 11 cases, grade 2 in 24 cases and grade 3 in 23 cases. Besides, the resected tumor samples of 20 patients with benign peripheral nerve tumor （10 cases of nerve sheath tumor and 10 cases of neurofibromatosis） and the normal peripheral nerves （by-products of some surgeries） of 5 patients were also collected. The samples were used with the approval of the patients. Rat-anti-human MMP-9, TIMP-1 monoclonal antibody and S-P kit were purchased from Fuzhou Maixin Biotechnology, Co.,Ltd. METHODS： The documented paraffin blocks were again prepared to sections of 5 lJ m. The expressions of MMP-9 and TIMP-1 in the samples were detected with mmunohistochemical S-P method. The relationships of the MPNST severity, recurrence, metastasis and survival rate with the expressions of MMP-9 and TIMP-1 were analyzed. MAIN OUTCOME MEASURES： Relationships of MMP-9 and TIMP-1 expressions with the MPNST severity and prognosis. RESULTS： ①Expressions of MMP-9 and TIMP-1 in three tissues： MMP-9 and TIMP-1 stainings were mainly observed in cytoplasm. Among the 58 MPNST patients, the MMP-9 expression was significantly higher than those in normal peripheral nerve and benign tumor （P 〈 0.05）, while the TIMP-1 expression in MPNST was lower than those in normal peripheral nerve and benign tumor （P 〈 0.05）. ②Relationship of MMP-9 and TIMP-1 expressions with the severity and prognosis of MPNST： The expressions of both proteins were observed in the four subtypes. The positive expression of MMP-9 in the MPNST patients of grades 2 - 3 was significantly higher than that in the MPNST patients of grade 1 （P 〈 0.05）, while the expression of MMP-9 was significantly lower than that in the MPNST patients of grade 1 （P 〈 0.05）. The metastatic rate was positively correlated with MMP-9 expression （r =1.696, P 〈 0.05）, but negatively correlated with TIMP-1 expression （r = - 2.125, P 〈 0.05）. CONCLUSION： MMP-9 and TIMP-1 are associated with MPNST pathological grades and metastasis, and can be used as the indicators for judging the severity and orognosis of MPNST.
文摘In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.
