氯沙坦对压力超负荷小鼠心肌肥厚和高迁移率族蛋白B1表达的影响  

Effects of Losartan on Both Pressure Overload-induced Cardiac Hypertrophy and the Expression of High-mobility Group Box 1 Expression

作　　者：张磊 张宝丽 吴剑 邹云增 姜红 葛均波 ZHANG Lei;ZHANG Bao-li;WU Jian;ZOU Yun-zeng;JIANG Hong;GE Jun-bo(Department of Cardiology,Shanghai Institute of Cardiovascular Diseases,Zhongshan Hospital of Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院心内科上海市心血管疾病研究所,上海市200032

出　　处：《中国分子心脏病学杂志》2020年第2期3330-3334,共5页Molecular Cardiology of China

基　　金：国家自然科学基金项目(81970375,81521001,81400193)

摘　　要：目的探讨氯沙坦对压力超负荷小鼠心肌肥厚和高迁移率族蛋白B1(HMGB1)表达的影响及机制。方法采用主动脉弓缩窄(TAC)方法建立压力超负荷小鼠心肌肥厚模型,并将小鼠随机分为假手术组、TAC+生理盐水组、TAC+氯沙坦组。术后2周行心脏超声检测并分析心肌组织学变化。同时,检测小鼠血清和心肌组织中HMGB1基因和蛋白表达水平,并检测心肌组织中细胞外信号调节激酶(ERK1/2)、P38和核转录因子(NF-κB)的表达及活化水平。结果TAC小鼠术后2周出现心肌肥厚,且氯沙坦可有效改善由TAC导致的左心室室壁增厚(P<0.05)。同时,TAC不仅升高小鼠血清HMGB1水平(P<0.05),还增加心肌HMGB1 mRNA和蛋白表达(P<0.05),而这些变化都可以被氯沙坦部分抑制(P<0.05)。此外,TAC导致心肌组织中p-ERK1/2、p-P38、p-NF-κB水平明显升高(P<0.05),且同样可以被氯沙坦部分抑制(P<0.05)。结论氯沙坦在改善压力超负荷所致心肌肥厚时伴随HMGB1表达减少,该作用可能与其阻断丝裂原活化蛋白激酶家族(MAPKs)及NF-κB信号通路有关。Objective To explore the effects of losartan on pressure overload-induced cardiac hypertrophy and high-mobility group box 1(HMGB1)expression.Methods Pressure overload models were built by transverse aortic constriction(TAC)in mice.The mice were divided into three groups:sham group,TAC+normal saline(NS)group and TAC+losartan group.Echocardiography measurement and histological analyses were performed at two weeks after the operation.Meanwhile,both the serum and cardiac expression of HMGB1 were detected.Moreover,the activities of extracellular signal-regulated kinase 1/2(ERK1/2),P38 and nuclear factor kappa-B(NF-κB)in myocardium were also examined.Results Cardiac hypertrophy were observed in mice after two weeks of TAC,which were ameliorated by losartan treatment(P<0.05).Meanwhile,both the serum levels of HMGB1 and the cardiac HMGB1 mRNA and protein expression were increased by TAC(P<0.05),which could also be inhibited by losartan treatment(P<0.05).Likewise,TAC upregulated the cardiac expression of p-ERK1/2,p-P38 and p-NF-κB(P<0.05),which were prohibited by the treatment of losartan(P<0.05).Conclusion Losartan ameliorates pressure overload-induced cardiac hypertrophy,along with the inhibition of HMGB1 expression,which might be mediated by prohibiting mitogen-activated protein kinases(MAPKs)and NF-κB signaling pathways.

关 键 词：压力超负荷 心肌肥厚 氯沙坦 高迁移率族蛋白B1 

分 类 号：R542.2[医药卫生—心血管疾病]