丹参酮Ⅱ_A对脂多糖诱导的H9c2心肌细胞损伤及ERK/Nrf2/HO-1通路的影响  

Effects of TanshinoneⅡA on Lipopolysaccharide-induced H9c2 Cardiomyocyte Injury and ERK/Nrf2/HO-1 Pathway

作　　者：王军[1] 李海红 杨洋 黄珊[1] Wang Jun;Li Haihong;Yang Yang;Huang Shan(Department of Cardiology,the First Affiliated Hospital of Hainan Medical College,Haikou 570100,China;Department of Critical Care Medicine,Hongqi Hospital Affiliated to Mudanjiang Medical College)

机构地区：[1]海南医学院第一附属医院心内科,海口570100 [2]牡丹江医学院附属红旗医院重症医学科

出　　处：《中国药师》2019年第8期1407-1410,1420,共5页China Pharmacist

基　　金：海南省高等学校科学研究项目(编号:Hnky2015-33)

摘　　要：目的:探究丹参酮ⅡA(TanⅡA)对脂多糖(LPS)诱导的H9c2心肌细胞损伤的作用,及其潜在的分子作用机制。方法:TanⅡA(5,10,20μmol·L^-1)处理大鼠H9c2心肌细胞,10μg·ml^-1LPS诱导建立心肌细胞损伤模型。CCK8法检测H9c2心肌细胞增殖情况。流式细胞术检测H9c2心肌细胞凋亡情况,蛋白免疫印迹(WB)检测H9c2心肌细胞外调节蛋白激酶(ERK)、磷酸化细胞外调节激酶(p-ERK)、核转录因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)蛋白水平,荧光法检测细胞内活性氧(ROS)水平。结果:与正常对照组相比,LPS模型组细胞增殖能力、p-ERK、核内Nrf2、HO-1蛋白水平降低,细胞凋亡率、核外Nrf2、ROS表达水平升高(P<0.05)。与LPS模型组相比,TanⅡ_A低剂量组细胞增殖、p-ERK、核内Nrf2、HO-1蛋白水平升高,细胞凋亡率、核外Nrf2蛋白表达水平降低(P<0.05);TanⅡA中、高剂量组细胞增殖、p-ERK、核内Nrf2、HO-1蛋白水平升高,细胞凋亡率、核外Nrf2、ROS表达水平降低(P<0.05)。各组EPK差异无统计学意义(P>0.05)。结论:TanⅡA对LPS诱导的H9c2心肌细胞损伤具有保护作用,可能通过激活ERK/Nrf2/HO-1通路信号实现,为TanⅡA应用于LPS诱导的心肌细胞损伤治疗提供一定的参考依据。Objective: To investigate the effect of tanshinone ⅡA(Tan ⅡA) on lipopolysaccharide(LPS)-induced H9 c2 cardiomyocyte injury and its potential molecular mechanism.Methods: Rat H9c2 cardiomyocytes were respectively treated with 5,10 and 20μmol·L^-1 Tan ⅡA,and induced by 10 μg·ml^-1 LPS to establish a cardiomyocyte injury model.CCK8 method was used to detect the proliferation of H9 c2 myocardial cells.Flow cytometry was used to detect the apoptosis of H9c2 myocardial cells,the levels of extracellular regulated protein kinase(ERK),phosphorylated extracellular regulated kinase(p-ERK),transcription factor NF-E2 related factor 2(Nrf2) and heme oxygenase 1(HO-1) in H9 c2 myocardium were detected by Western blot(WB),and the levels of reactive oxygen species(ROS) in cells were measured by fluorescence method.Results: Compared with those in the blank group,the proliferation ability,p-ERK,intranuclear Nrf2 and HO-1 protein levels in LPS group were significantly decreased,and the apoptotic rate,extranu-clear Nrf2 protein level and ROS were significantly increased(P<0.05).Compared with those in LPS group,the cell proliferation,p-ERK,intranu-clear Nrf2 and HO-1 protein levels in Tan ⅡA low dose group increased significantly,while the apoptotic rate,extranuclear Nrf2 protein expression and ROS decreased significantly(P<0.05);the cell proliferation,p-ERK,intranuclear Nrf2 and HO-1 protein levels in Tan ⅡA medium and high dose groups increased significantly,while the apoptotic rate and extranuclear Nrf2 protein expression decreased significantly(P<0.05).There was no significant difference in ERK among groups(P > 0.05).Conclusion: Tan ⅡA has protective effect on LPS-induced H9 c2 cardiomyocyte injury,and the effect may be achieved by regulating ERK/Nrf2/HO-1 signal,which provides reference for Tan II A in the treatment of LPS-induced cardiomyocyte injury.

关 键 词：丹参酮ⅡA 脂多糖 H9C2心肌细胞 细胞外调节蛋白激酶 核转录因子E2相关因子2 血红素加氧酶1 

分 类 号：R965.1[医药卫生—药理学]