目的:通过盲肠穿刺结扎法建立脓毒症大鼠模型,观察四逆汤是否可以改善脓毒症SD大鼠肾损伤,探讨四逆汤是否通过抑制NLRP3-Caspase-1-IL-1β/IL-18信号通路改善脓毒症SD大鼠肾损伤。方法:100只雌性大鼠,按照大鼠体重进行初步分类,采用轮...目的:通过盲肠穿刺结扎法建立脓毒症大鼠模型,观察四逆汤是否可以改善脓毒症SD大鼠肾损伤,探讨四逆汤是否通过抑制NLRP3-Caspase-1-IL-1β/IL-18信号通路改善脓毒症SD大鼠肾损伤。方法:100只雌性大鼠,按照大鼠体重进行初步分类,采用轮次分配法,确保每组大鼠体重分布均匀。平均分成3大组,每组30只老鼠,从中随机选取1组作为空白组,剩下两组使用CLP法进行造模,分别是实验组、对照组两个大组。随后又分别按大鼠体重采用轮次分类分为8小时组、16小时组和24小时组三个小组,每个小组10只;其中死亡10只,继续造模补充;实验组采用四逆汤灌胃、对照组和空白组采用生理盐水灌胃。分别在8 h、16 h、24 h时间点,取各组大鼠肾组织进行HE染色,计算肾损伤评分,WB检测肾组织中NLRP3、Caspase-1蛋白表达,ELISA法检测血清IL-1β、IL-18表达情况。结果:1) 肾组织HE染色后高倍镜下对照组8小时开始可见肾脏正常形态被破坏,肾小球体积明显增大,肾小囊腔扩大,系膜细胞肿胀、间质炎性细胞浸润;16小时较8小时更加严重,并且间质有明显出血及大量炎症细胞浸润;24小时肾小球缺血皱缩,失去正常形态;球–囊间隙扩大,炎性细胞渗出增多,肾小管上皮细胞肿胀。实验组大鼠8小时及16小时的肾脏病理改变较对照组明显减轻。肾损伤评分中,肾损伤随着时间的延长而逐渐加重(P P P P > 0.05)。3) ELISA检测血清IL-1β、IL-18后发现,总趋势是从8小时开始明显上升(P P P > 0.05)。这与WB检查结果相似。结论:四逆汤可能通过介导NLRP3-Caspase-1-IL-1β/IL-18信号通路改善脓毒症急性肾损伤SD大鼠肾损伤。Objective: Sepsis rat model was established by cecal puncture and ligation to observe whether Sini Decoction could improve kidney injury of septic SD rats, and to explore whether Sini Decoction could improve kidney injury of septic SD rats by inhibiting NLRp3-caspase-1-IL-1β/IL-18 signaling pathway. Methods: 100 female rats, initially classified according to the weight of the rats, using a round-robin allocation method to ensure an even distribution of weights in each group. Divided into 3 large groups on average, each group of 30 rats, from which 1 group was randomly selected as the blank, and the remaining two groups were used for modeling with the CLP method. A total of 100 female rats were initially classified according to their body weights. The round-robin allocation method was used to ensure a uniform distribution of body weights among each group. The rats were evenly divided into three major groups, with 30 rats in each group. One group was randomly selected as the blank group, and the remaining two groups were used to establish the model using the CLP method, namely the experimental group and the control group. Subsequently, according to the body weights of the rats, each of these two groups was further divided into three subgroups (8-hour group, 16-hour group, and 24-hour group) using the round-robin classification method, with 10 rats in each subgroup. Ten rats died during the process, and new rats were used to continue the modeling to make up for the loss. The experimental group was administered Sini Decoction by gavage, while the control group and the blank group were administered normal saline by gavage. At the time points of 8 h, 16 h, and 24 h, the renal tissues of the rats in each group were collected for HE staining, and the renal injury score was calculated. Western blotting (WB) was used to detect the protein expressions of NLRP3 and Caspase-1 in the renal tissues, and the enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of serum IL-1β and IL-18. Results: 1) After HE staining of the renal tissues, under a high-power microscope, in the control group, the normal morphology of the kidneys was found to be damaged starting from 8 hours, with a significant increase in the volume of the glomeruli, expansion of the renal capsule cavity, swelling of the mesangial cells, and infiltration of interstitial inflammatory cells. The situation at 16 hours was more severe than that at 8 hours, with obvious interstitial bleeding and a large number of inflammatory cell infiltrations. At 24 hours, the glomeruli were ischemic and shrunk, losing their normal morphology;the glomerular-capsular space was enlarged, the exudation of inflammatory cells increased, and the tubular epithelial cells were swollen. The renal pathological changes in the experimental group at 8 hours and 16 hours were significantly milder than those in the control group. In the renal injury score, the renal injury gradually worsened over time (P P P P > 0.05). 3) Serum IL-1β and IL-18 were detected by ELISA, and they began to increase at 8 h (P P P > 0.05). This is similar to the WB results. Conclusion: Sini Decoction may improve renal function in SD rats with sepsis acute kidney injury by mediating NLRP3-Caspase-1-IL-1β/IL-18 signaling pathway.展开更多
目的观察喘可治注射液(CKZ)对慢性阻塞性肺疾病(COPD)大鼠肺组织IL-12/IL-12R/STAT4信号通路的影响。方法 50只SD大鼠随机分为正常组,模型组,CKZ高、中、低剂量(CKZ-H、CHZ-M、CKZ-L)组。除正常组外,各组复制COPD大鼠模型,并给予相应药...目的观察喘可治注射液(CKZ)对慢性阻塞性肺疾病(COPD)大鼠肺组织IL-12/IL-12R/STAT4信号通路的影响。方法 50只SD大鼠随机分为正常组,模型组,CKZ高、中、低剂量(CKZ-H、CHZ-M、CKZ-L)组。除正常组外,各组复制COPD大鼠模型,并给予相应药物治疗,观察CKZ对COPD大鼠血清和肺泡灌洗液(BALF)中γ-干扰素(IFN-γ)、白细胞介素12(IL-12)、白细胞介素12受体(IL-12R)以及肺组织信号转导子和转录激活子4(STAT4)m RNA表达的影响。结果喘可治注射液各剂量组肺组织病理形态均有不同程度的改善,且降低COPD大鼠血清和BALF中IFN-γ、IL-12、IL-12R(除CKZ-L组BALF中IL-12R外)水平(P<0.05,P<0.01),可抑制大鼠肺组织STAT4 m RNA的表达(P<0.01,P<0.05)。结论喘可治注射液能一定程度改善COPD大鼠肺组织病理损害,其作用机制可能与其抑制IFN-γ、IL-12、IL-12R表达,干扰IL-12/IL-12R/STAT4信号通路对靶基因的激活,下调STAT4 m RNA表达,进而调节Th1/Th2分化失衡有关。展开更多
To identify the roles of serum IL-18, IL- 10, TNF-α and sIL-2R in the pathogenisis of chronic hepatitis C and the effects of interferon on the men- tioned serum cytokines. Methods: The levels of IL-18, IL-10, TNF-α ...To identify the roles of serum IL-18, IL- 10, TNF-α and sIL-2R in the pathogenisis of chronic hepatitis C and the effects of interferon on the men- tioned serum cytokines. Methods: The levels of IL-18, IL-10, TNF-α and sIL-2R were detected in 10 healthy controls, 24 a- symptomatic HCV carriers, and 27 patients with chronic hepatitis C (before and after IFN treatment) by enzyme linked immunosorbent assay (ELISA). Results: The levels of IL-18, IL-10, TNF-α and sIL- 2R in the patients of chronic hepatitis C were higher than those in the healthy controls (P<0.05) and in asymptomatic HCV carriers (P<0. 05). The values of the mentioned cytokines showed a significant posi- tive correlation to GPT. The levels of the mentioned cytokines decreased obviously after IFN treatment (P <0. 05), while the serum levels of IL-10 and sIL-2R reduced in sequence in no-response group, partial- response group and complete-response group. Conclusions: IL-18, IL-10, TNF-α and sIL-2R co- participate in the pathogenisis of chronic hepatitis C, and are used to evaluate the effect of IFN on the im- mune state of organisms, and IL-10 and sIL-2R are important for predicting the anti-viral efficacy of IFN.展开更多
文摘目的:通过盲肠穿刺结扎法建立脓毒症大鼠模型,观察四逆汤是否可以改善脓毒症SD大鼠肾损伤,探讨四逆汤是否通过抑制NLRP3-Caspase-1-IL-1β/IL-18信号通路改善脓毒症SD大鼠肾损伤。方法:100只雌性大鼠,按照大鼠体重进行初步分类,采用轮次分配法,确保每组大鼠体重分布均匀。平均分成3大组,每组30只老鼠,从中随机选取1组作为空白组,剩下两组使用CLP法进行造模,分别是实验组、对照组两个大组。随后又分别按大鼠体重采用轮次分类分为8小时组、16小时组和24小时组三个小组,每个小组10只;其中死亡10只,继续造模补充;实验组采用四逆汤灌胃、对照组和空白组采用生理盐水灌胃。分别在8 h、16 h、24 h时间点,取各组大鼠肾组织进行HE染色,计算肾损伤评分,WB检测肾组织中NLRP3、Caspase-1蛋白表达,ELISA法检测血清IL-1β、IL-18表达情况。结果:1) 肾组织HE染色后高倍镜下对照组8小时开始可见肾脏正常形态被破坏,肾小球体积明显增大,肾小囊腔扩大,系膜细胞肿胀、间质炎性细胞浸润;16小时较8小时更加严重,并且间质有明显出血及大量炎症细胞浸润;24小时肾小球缺血皱缩,失去正常形态;球–囊间隙扩大,炎性细胞渗出增多,肾小管上皮细胞肿胀。实验组大鼠8小时及16小时的肾脏病理改变较对照组明显减轻。肾损伤评分中,肾损伤随着时间的延长而逐渐加重(P P P P > 0.05)。3) ELISA检测血清IL-1β、IL-18后发现,总趋势是从8小时开始明显上升(P P P > 0.05)。这与WB检查结果相似。结论:四逆汤可能通过介导NLRP3-Caspase-1-IL-1β/IL-18信号通路改善脓毒症急性肾损伤SD大鼠肾损伤。Objective: Sepsis rat model was established by cecal puncture and ligation to observe whether Sini Decoction could improve kidney injury of septic SD rats, and to explore whether Sini Decoction could improve kidney injury of septic SD rats by inhibiting NLRp3-caspase-1-IL-1β/IL-18 signaling pathway. Methods: 100 female rats, initially classified according to the weight of the rats, using a round-robin allocation method to ensure an even distribution of weights in each group. Divided into 3 large groups on average, each group of 30 rats, from which 1 group was randomly selected as the blank, and the remaining two groups were used for modeling with the CLP method. A total of 100 female rats were initially classified according to their body weights. The round-robin allocation method was used to ensure a uniform distribution of body weights among each group. The rats were evenly divided into three major groups, with 30 rats in each group. One group was randomly selected as the blank group, and the remaining two groups were used to establish the model using the CLP method, namely the experimental group and the control group. Subsequently, according to the body weights of the rats, each of these two groups was further divided into three subgroups (8-hour group, 16-hour group, and 24-hour group) using the round-robin classification method, with 10 rats in each subgroup. Ten rats died during the process, and new rats were used to continue the modeling to make up for the loss. The experimental group was administered Sini Decoction by gavage, while the control group and the blank group were administered normal saline by gavage. At the time points of 8 h, 16 h, and 24 h, the renal tissues of the rats in each group were collected for HE staining, and the renal injury score was calculated. Western blotting (WB) was used to detect the protein expressions of NLRP3 and Caspase-1 in the renal tissues, and the enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of serum IL-1β and IL-18. Results: 1) After HE staining of the renal tissues, under a high-power microscope, in the control group, the normal morphology of the kidneys was found to be damaged starting from 8 hours, with a significant increase in the volume of the glomeruli, expansion of the renal capsule cavity, swelling of the mesangial cells, and infiltration of interstitial inflammatory cells. The situation at 16 hours was more severe than that at 8 hours, with obvious interstitial bleeding and a large number of inflammatory cell infiltrations. At 24 hours, the glomeruli were ischemic and shrunk, losing their normal morphology;the glomerular-capsular space was enlarged, the exudation of inflammatory cells increased, and the tubular epithelial cells were swollen. The renal pathological changes in the experimental group at 8 hours and 16 hours were significantly milder than those in the control group. In the renal injury score, the renal injury gradually worsened over time (P P P P > 0.05). 3) Serum IL-1β and IL-18 were detected by ELISA, and they began to increase at 8 h (P P P > 0.05). This is similar to the WB results. Conclusion: Sini Decoction may improve renal function in SD rats with sepsis acute kidney injury by mediating NLRP3-Caspase-1-IL-1β/IL-18 signaling pathway.
文摘目的观察喘可治注射液(CKZ)对慢性阻塞性肺疾病(COPD)大鼠肺组织IL-12/IL-12R/STAT4信号通路的影响。方法 50只SD大鼠随机分为正常组,模型组,CKZ高、中、低剂量(CKZ-H、CHZ-M、CKZ-L)组。除正常组外,各组复制COPD大鼠模型,并给予相应药物治疗,观察CKZ对COPD大鼠血清和肺泡灌洗液(BALF)中γ-干扰素(IFN-γ)、白细胞介素12(IL-12)、白细胞介素12受体(IL-12R)以及肺组织信号转导子和转录激活子4(STAT4)m RNA表达的影响。结果喘可治注射液各剂量组肺组织病理形态均有不同程度的改善,且降低COPD大鼠血清和BALF中IFN-γ、IL-12、IL-12R(除CKZ-L组BALF中IL-12R外)水平(P<0.05,P<0.01),可抑制大鼠肺组织STAT4 m RNA的表达(P<0.01,P<0.05)。结论喘可治注射液能一定程度改善COPD大鼠肺组织病理损害,其作用机制可能与其抑制IFN-γ、IL-12、IL-12R表达,干扰IL-12/IL-12R/STAT4信号通路对靶基因的激活,下调STAT4 m RNA表达,进而调节Th1/Th2分化失衡有关。
文摘To identify the roles of serum IL-18, IL- 10, TNF-α and sIL-2R in the pathogenisis of chronic hepatitis C and the effects of interferon on the men- tioned serum cytokines. Methods: The levels of IL-18, IL-10, TNF-α and sIL-2R were detected in 10 healthy controls, 24 a- symptomatic HCV carriers, and 27 patients with chronic hepatitis C (before and after IFN treatment) by enzyme linked immunosorbent assay (ELISA). Results: The levels of IL-18, IL-10, TNF-α and sIL- 2R in the patients of chronic hepatitis C were higher than those in the healthy controls (P<0.05) and in asymptomatic HCV carriers (P<0. 05). The values of the mentioned cytokines showed a significant posi- tive correlation to GPT. The levels of the mentioned cytokines decreased obviously after IFN treatment (P <0. 05), while the serum levels of IL-10 and sIL-2R reduced in sequence in no-response group, partial- response group and complete-response group. Conclusions: IL-18, IL-10, TNF-α and sIL-2R co- participate in the pathogenisis of chronic hepatitis C, and are used to evaluate the effect of IFN on the im- mune state of organisms, and IL-10 and sIL-2R are important for predicting the anti-viral efficacy of IFN.
