肝硬化大鼠肝部分切除后IL-6/STAT3信号通路的变化

Changes in IL-6/STAT3 signal pathway after partial hepatectomy in rats with cirrhosis

目的了解白细胞介素-6(IL-6)/信号转导及转录活化因子3(STAT3)信号通路在肝硬化大鼠肝部分切除后残肝再生障碍中的作用。方法采用皮下注射四氯化碳(CCl4)法建立肝硬化大鼠模型。正常大鼠为对照组。对照组及肝硬化组均行70%肝切除后,于不同的时间点收集残肝组织及血液标本,检测血清IL-6、肿瘤坏死因子-α(TNF-α)水平、肝组织增殖细胞核抗原(PCNA)及活性STAT3蛋白表达。结果肝切除后24 h,肝硬化组大鼠有丝分裂细胞数及PCNA阳性细胞数均明显小于对照组。肝切除后的前12 h,肝硬化组大鼠IL-6表达水平明显低于对照组。术后2 h,对照组残肝组织的活性STAT3蛋白远远高于肝硬化组。结论肝硬化肝切除术后早期IL-6的低表达导致STAT3蛋白活化不足是肝硬化大鼠肝部分切除术后残肝再生障碍的重要原因之一。

Objective To analyze the changes of IL-6/STAT3 signal pathway after partial hepatectomy in rats with CCl4-induced cirrhosis.Methods Cirrhosis was induced in rats by hypodermic injection of CCl4.Untreated rats were used as controls.The control rats and the cirrhotic rats were subjected to 70% partial hepatectomy.At different time points after hepatectomy,the residual liver and blood samples were collected,the levels of IL-6 and TNF-α in serum,the expression of PCNA and active STAT3 proteins in the liver tissue were analyzed.Results 24 h after hepatectomy,we detected significantly lower mitotic index and PCNA positive cells in the cirrhotic rat as compared to the controls.The cirrhotic rat expressed significantly lower levels of IL-6 as compared to the controls up to 12 h after hepatectomy.Significantly lower levels of active STAT3 proteins were also observed in the cirrhotic rat 2 h after hepatectomy.Conclusion The data from our study shows that one of the most important reasons for the impaired liver regeneration in cirrhotic remnants is associated with low expression of IL-6 in the early stage and the following low activation of STAT3 proteins.