保肝宁对肝纤维化模型大鼠肝组织形态学及JAK2、STAT3蛋白磷酸化水平的影响  

Influence of "Bao Gan Ning" on Liver Histomorphology and Protein Phosphorylation Levels of JAK2 and STAT3 of Liver Fibrosis Rats

作　　者：贺松其[1] 文彬[2] 吕志平[1] 侯丽颖[1] 

机构地区：[1]南方医科大学中医药学院,广东广州510515 [2]解放军四五八医院老干科,广东广州510602

出　　处：《上海中医药杂志》2008年第5期75-79,共5页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助课题(30672769);广东省中医药局基金资助课题(1050128)

摘　　要：目的探讨保肝宁抗肝纤维化的作用机制。方法采用复合因素建立肝纤维化大鼠模型。将50只大鼠随机分为正常对照组、模型组、秋水仙碱组、保肝宁大剂量组、保肝宁中剂量组,各组均10只,观察各组大鼠的一般情况及肝脾指数的变化,光镜下观察肝组织病理学变化及肝纤维化程度分级比较,采用Western Blot法检测肝脏组织细胞内JAK2、STAT3蛋白磷酸化表达水平。结果与模型组比较,保肝宁能显著降低模型大鼠肝、脾指数,差异有显著性意义(P均<0.01);与模型组比较,保肝宁能显著减轻模型大鼠肝组织纤维化的病理程度(P均<0.01);与正常组比较,模型组、各药物组JAK2、STAT3蛋白磷酸化水平表达程度均增高;与模型组相比,各药物组的JAK2、STAT3蛋白磷酸化水平表达明显降低;保肝宁大、中剂量组和秋水仙碱组相比,JAK2、STAT3蛋白磷酸化水平明显降低。结论保肝宁可有效降低模型大鼠肝、脾指数,显著减轻模型大鼠肝组织纤维化的病理程度。其作用机理可能与下调JAK2、、STAT3蛋白磷酸化水平,抑制JAK2/STAT3信号通路,从而达到直接抑制HSC活化相关,最终达到抗肝纤维化的目的。Objective To discuss the mechanisms of ＂Bao Gan Ning＂ against liver fibrosis. Methods Compound factors were adopted to set up fibrosis rat model, and 50 fibrosis rats were randomized into 5 groups： normal control, model, colchicine and large- and medium-dose of ＂Bao Gan Ning＂ groups, 10 rats in each group. Observe the changes of general condition and hepatosplenic index of model rats, and the pathological changes in liver tissue by optical microscope, with the grading comparison of liver fibrosis degrees. Employ Western Blot to detect the protein phosphorylation expression level of JAK2 and STAT3 in liver cells. Results Compared with model group, ＂Bao Gan Ning＂ could apparently lower the hepatosplenic index of liver fibrosis model rat, with notable significances in their differences （P〈 0.01）, and evidently lower the pathological level of liver fibrosis of model rat （P〈 0.01）. Compared with the normal group, the expression levels of protein phosphorylation of JAK2 and STAT3 rose in the model and drug groups. In the drug groups, the levels decreased significantly compared with the model. Meanwhile, the expression level also decreased evidently in the large- and medium-dose of ＂Bao Gan Ning＂ groups compared with the colchicines. Condusion ＂Bao Gan Ning＂ can effectively reduce the hepatosplenic index of liver fibrosis model rat, and obviously lower the pathological level of liver fibrosis of model rat, whose mechanism may be related with the reduction of protein phosphorylation level of JAK2 and STAT3, the inhibition of JAK2/STAT signal pathway, and the direct suppression of HSC activation, consequently to fight against liver fibrosis.

关 键 词：肝纤维化 模型大鼠 保肝宁 肝脾指数 瘦素 

分 类 号：R285[医药卫生—中药学]