肾气丸对非酒精性脂肪性肝炎大鼠Bcl－2／Bax、Fas／FasL信号通路的影响

摘要

Objective:To explore the role of the signaling transduction pathway of Bcl-2/Bax and Fas/FasL on nonalcoholic steatohepati-tis( NASH) induced by high fat diet in rats and the effects of Shenqi pill on the signaling pathway.Methods:The model rats of NASH were induced by 12 weeks high-fat diet, and treated with Shenqi pill.Pathological histology of rats liver was observed with HE staining.Protein expression of Fas, FasL, Bcl-2, Bax and Caspase-8 in liver were measured by IHC.Expression of Caspase-8 mRNA in liver was measured by Realtime-PCR.Results:The protein expression of Bcl-2,Bax,Fas,FasL and Caspase-8 and the expression of Caspase-8 mRNA in rats liver in the model group were remarkably higher than those in the normal group(P<0.01), the ratio of Bcl-2 and Bax were significantly reduced (P<0.05), the protein expression of Caspase-8 in rats liver showed positive correlation with the protein expression of Fas,FasL(r values re-spectively 0.907, 0.804, P all less than 0.01 ).After the treatment of Shenqi pill, the protein expression of Bax, Fas, FasL and Caspase-8 and the expression of Caspase-8 mRNA were obviously reduced than those in the model( P<0.05 ) , the ratio of Bcl-2/Bax was obviously higher than that in the model, the protein expression of Bcl-2 showed no significance with the model(P>0.05).Conclusion:Shenqi pill ob-viously depress protein expression of Bax, Fas, FasL and Caspase-8 in liver and decrease the hepatocyte lipid apoptosis by affecting Bcl-2/Bax and Fas/FasL signaling transduction pathway, and prevent the further development of NASH.%目的：观察Bcl－2／Bax、Fas／FasL介导的信号转导通路在高脂饮食诱导的非酒精性脂肪性肝炎大鼠的作用及肾气丸对其的影响。方法：采用高脂饲料连续喂养12周建立大鼠非酒精性脂肪性肝炎模型，同时以肾气丸进行干预12周。 HE染色观察大鼠肝组织病理组织学变化，免疫组织化学检测肝组织中Fas、FasL、Bcl－2、Bax、Caspase－8蛋白的表达； Realtime－PCR法检测肝组织Caspase－8 mRNA表达。结果：模型组大鼠肝组织Bcl－2、Bax、Fas、FasL蛋白以及Caspase－8 mRNA和蛋白表达均较正常组显著增加（P＜0．01），Bcl－2／Bax比值较正常组明显的降低（P＜0．05）；大鼠肝组织Caspase－8蛋白表达与Fas、FasL蛋白表达均呈明显正相关（ r分别为0．907、0．804，P均＜0．01）；予以肾气丸干预后，Bax、Fas、FasL蛋白的表达以及Caspase－8 mRNA和蛋白的表达均较模型组明显的降低（P＜0．05），Bcl－2／Bax比值较模型组明显的增加（P＜0．05），Bcl－2蛋白的表达与模型组比较差异无显著性意义（P＞0．05）。结论：肾气丸可能通过影响Bcl－2／Bax、Fas／FasL信号转导通路，下调Bax、Fas、FasL、Caspase－8表达，减少肝细胞的脂性凋亡，从而防治大鼠非酒精性脂肪性肝炎的发生发展。