小柴胡汤下调JAK2,STAT3的表达治疗大鼠肝纤维化

Xiaochaihu Tang Depress Expression of JAK2 and STAT3 of Liver Fibrosis in Rats

目的:探讨小柴胡汤对大鼠肝纤维化过程中肝组织Janus激酶2(Janus kinase 2,JAK2)及信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)表达的影响。方法:健康SD雄性大鼠,适应性喂养1周后随机分为5组,空白对照组,模型组,小柴胡汤高、中、低(4,2,1 g·kg-1)剂量组。模型组大鼠采用10%四氯化碳皮下注射,每周2次制备大鼠肝纤维化模型共14周,于造模第9周小柴胡汤各剂量组给予小柴胡汤灌胃治疗6周。通过测定血清中丙氨酸转氨酶(ALT)及天冬氨酸转氨酶(AST)活性反映肝脏功能,HE染色法观察肝组织病理学变化,免疫组化方法观察肝组织金属蛋白酶组织抑制因子-1(tissue inhibitor of metalloproteinase-1,TIMP-1)的表达,Real-time RT-PCR检测JAK2,STAT3 mRNA的表达。结果:与空白对照组比较,四氯化碳诱导的肝纤维大鼠外周血ALT,AST明显升高,病理学呈现肝纤维化表现;肝脏组织TIMP-1,JAK2和STAT3表达明显升高(P<0.05或P<0.01)。与模型组相比,小柴胡汤中、高剂量组在血清学和病理学上均有明显改善;与模型组相比,小柴胡汤高剂量组肝组织TIMP-1表达明显降低,小柴胡汤中、高剂量组JAK2,STAT3 mRNA的表达明显降低(P<0.05或P<0.01)。结论:小柴胡汤可下调JAK2和STAT3的表达参与对大鼠肝纤维化的治疗。

Objective：To explore the expression of Janus kinase 2 （JAK2） and signal transducer and activator of transcription 3 （STAT3） in hepatic fibrosis rat model impacted by Xiaochaihu Tang.Method：Hepatic fibrosis model was induced by 10％ CCl4 for 9 weeks in rat.The rats were treated by Xiao Chaihu Tang for 6 weeks at the beginning of the 9th week.Alanine aminotransferase （ALT） and aspartate aminotransferase （AST）in serum were measured to reflect liver function.The pathological characteristics of hepatic tissues were detected by HE staining.Tissue inhibitor of metalloproteinase-1 was observed by immunohistochemistry.The expression of JAK2 and STAT3 mRNA was detected by real-time RT-PCR.Result：Compared with the model group,serology and histology showed significant improvement.TIMP-1 was reduced in the high-dose group of Xiaochaihu Tang compared with the model group and the expression of JAK2 and STAT3 was downregulated obviously in the middledose group （P ＜ 0.05） and the high-dose group （P ＜ 0.01）.Conclusion：Xiaochaihu Tang can improve the liver fibrosis induced by CCl4 and depress the expression of JAK2 and STAT3 in rat.