摘要
目的探讨肿瘤坏死因子受体p55/p75(TNFR p55/TNFR p75)在重症急性胰腺炎(SAP)发病机制中的作用。方法36只雄性SD大鼠均分为对照组与SAP组。SAP组采用5%牛黄胆酸钠1ml/kg胰胆管逆行穿刺注射建立模型,对照组仅给予剖腹假手术。两组大鼠分别在造模后3、6和12h处死,收集外周血与胰腺标本。ELISA法检测血清TNFα水平,RT PCR法检测外周血单个核细胞(PBMC)与胰腺组织中TNFR p55/TNFR p75mRNA表达,采用血清淀粉酶与病理组织学评分作为SAP严重程度的指标。结果SAP组不同时间点血清淀粉酶、TNFα水平及胰腺组织炎症评分均显著高于对照组(P<0.01)。在PBMC中TNFR p55/TNFR p75mRNA的表达在各时间点均较对照组显著上调(P值均<0.01),且在6h达峰值,分别为1.32±0.07和0.95±0.04;而对照组在6h点为0.84±0.01和0.68±0.04。胰腺组织中TNFR p55/TNFR p75mRNA的表达在各时间点也均高于对照组(P值均<0.05)。结论TNFα是SAP病程中重要的细胞因子并可能通过结合胰腺组织中TNFR p55/TNFR p75参与胰腺组织损伤;同时,TNFα又可能通过与PBMC中TNFR p55/TNFR p75相互作用导致外周血中白细胞活化,从而加重胰腺炎的严重程度。
Objective To investigate the effect of tumor necrosis factor receptor-p55/p75(TNFR-p55/ TNFR-p75) on the pathogenesis of severe acute pancreatitis (SAP) in rats. Methods Thirty-six male Sprague-Dawley rats were divided into 2 groups: SAP group and control group. SAP model was ~induced by injection of 5% sterile sodium taurocholate into biliopancreatic duct, while control group was only given sham operation. Rats were sacrificed at 3, 6, and 12 hours after the onset of operation. Blood sample and pancreatic tissues were collected. The severity of pancreatitis was assessed according to the level of serum amylase and histological scoring. The serum levels of tumor necrosis factor-α(TNF-α) were examined by ELISA. Expressions of TNFR-p55 mRNA and ~TNFR-p75 mRNA in pancreatic tissues and peripheral blood mononuclear cells (PBMC) were measured by semi-quantitative RT-PCR. Results The levels of serum amylase and TNF-α in SAP group were both significantly higher than those in the control group at each time point (P< 0.01,respectively). The expressions of TNFR-p55 mRNA and ~TNFR -p75 mRNA in both PBMC and pancreatic tissues of SAP group were significantly upregulated at each time point (P<0.01,P<0.05). Besides, the expression of TNFR in PBMC reached its maximum level at about 6 hours after the onset of SAP and then declined. Conclusions TNF-α is a pivotal factor in the pathogenesis of pancreatitis and its binding to TNFR-p55 and TNFR-p75 may initiate the pathological ~deterioration of pancreatic tissue. The present study also indicated a pathogenetic role of cytotoxic TNF in the clinical features of SAP by enhancing leucocyte activation through upregulation of TNFR-p55 and TNFR-p75 in both PBMC and pancreatic tissue.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2005年第3期138-141,共4页
Chinese Journal of Digestion
基金
上海市自然科学基金资助项目(01ZB14026)
关键词
肿瘤坏死因子受体
P55
P75
急性胰腺炎
发病机制
Severe acute pancreatitis
Tumor necrosis factor-α
Tumor necrosis factor receptor-p55
Tumor necrosis factor receptor-p75
