摘要
目的研究丹参酮ⅡA(tanshinoneⅡA,TanⅡA)对CCl_(4)诱导小鼠急性肝损伤的抗氧化、保护作用及其可能的作用机制。方法将C57BL/6J小鼠随机分成正常组、CCl_(4)组以及TanⅡA保护组(TanⅡA 20 mg/kg+CCl_(4)),每组10只。腹腔注射CCl_(4)构建小鼠急性肝损伤模型。计算各组小鼠的肝脏指数,检测血清AST和ALT活性,测定肝组织SOD活性及GSH、MDA含量,HE染色观察肝组织病理变化,免疫组织化学法和Western blot检测肝组织PI3K、p-PI3K、Akt、p-Akt、Nrf2和HO-1蛋白表达水平。结果与CCl_(4)组相比,TanⅡA保护组肝脏指数显著下降(P<0.01),血清AST(P<0.01)和ALT活性降低(P<0.05),肝组织SOD活性(P<0.01)及GSH含量升高(P<0.05),MDA含量降低(P<0.05),肝组织病理变化得到显著改善。同时,TanⅡA使肝组织p-PI3K和p-Akt表达水平明显升高(P<0.01),显著诱导Nrf2转位入核(P<0.01),促使其下游靶蛋白HO-1表达水平明显升高(P<0.01)。结论TanⅡA能够显著改善CCl_(4)诱导的急性肝损伤,其机制可能与PI3K/Akt/Nrf2/HO-1信号通路有关。
Objective To investigate the antioxidant and protective effect of tanshinone ⅡA(TanⅡA)on CCl_(4)-induced acute liver injury in mice and its possible mechanism.Methods C57BL/6J mice were randomly divided into a control group,a CCl_(4)group and a TanⅡA protective group(TanⅡA 20 mg/kg+CCl_(4)),with 10 mice in each group.Acute liver injury model was induced by intraperitoneal injection of CCl_(4)in mice.The liver indices were calculated,the activities of serum AST and ALT were detected,the activity of SOD and the contents of GSH and MDA in liver tissue were measured,and the pathological changes of liver tissue were observed by HE staining.The expression levels of PI3K,p-PI3K,Akt,p-Akt,Nrf2 and HO-1 proteins in liver tissue were detected by immunohistochemistry and Western blot.Results Compared with the CCl_(4)group,in the TanⅡA protective group,the liver indices was significantly decreased(P<0.01),the activities of serum AST(P<0.01)and ALT(P<0.05)was reduced,the activity of SOD(P<0.01)and the content of GSH(P<0.05)were increased while decreasing the content of MDA(P<0.05)in liver tissue,and the pathological changes of liver tissue was significantly improved.In addition,TanⅡA could significantly increase the expression levels of p-PI3K and p-Akt(P<0.01)in liver tissue,while significantly inducing Nrf2 translocation into nucleus(P<0.01),which significantly increased the expression level of its downstream target protein HO-1(P<0.01).Conclusions TanⅡA can significantly ameliorate CCl_(4)-induced acute liver injury.Its mechanism may be related to PI3K/Akt/Nrf2/HO-1 signaling pathway.
作者
李青青
熊佳慧
温玉清
杨红胜
李金斗
方萌
刘宇炜
Li Qingqing;Xiong Jiahui;Wen Yuqing;Yang Hongsheng;Li Jindou;Fang Meng;Liu Yuwei(School of Medicine,Jianghan University,Wuhan 430056,China)
出处
《中国临床解剖学杂志》
CSCD
北大核心
2022年第6期671-676,共6页
Chinese Journal of Clinical Anatomy
基金
国家自然科学基金面上项目(31371090)
湖北省卫生健康科研基金(WJ2021M217)
江汉大学2022年度大学生科研重点项目(2022zd053,2022zd059)。
