目的 探究神经调节蛋白1(neuregulin-1,NRG-1)对血管紧张素Ⅱ(angiotensin-Ⅱ,Ang-Ⅱ)诱导的心肌肥大的保护作用及其潜在机制.方法 体外培养大鼠心肌细胞系(H9C2),使用Ang-Ⅱ处理H9C2细胞,构建Ang-Ⅱ诱导的心肌肥大细胞模型.给予NRG-1干预H9C2细胞,通过测量心肌细胞表面积和活性氧(reactive oxygen species,ROS)含量,检测线粒体膜电位,通过 Western blot 法检测心房钠尿肽(atrial natriuretic peptide,ANP)、脑钠肽(brain natriuretic peptide,BNP)、沉默信息调节因子 1(silent information regulator 1,SIRT1)、超氧化物歧化酶 1(superoxide dismutase 1,SOD1)及 NADPH 氧化酶 2(NADPH oxidase isoform 2,NOX2)蛋白表达,观察NRG-1的保护作用.结果 与模型组比较,NRG-1能够明显降低心肌细胞表面积(P＜0.05),减少肥大标志物ANP、BNP表达(P＜0.05),降低ROS水平(P＜0.05),升高线粒体膜电位(P＜0.05),增加SOD1、SIRT1表达(P＜0.05),降低NOX2蛋白水平(P＜0.05).SIRT1抑制剂EX527可以阻断NRG-1的保护作用.结论 NRG-1可改善Ang-Ⅱ诱导的心肌细胞肥大,其潜在机制可能与SIRT1-NOX2氧化应激通路有关.
NRG-1 Attenuates Angiotensin-Ⅱ induced Myocardial Hypertrophy Via the SIRT1-NOX2 Pathway
Objective To investigate the protective effect of neuregulin-1(NRG-1)on myocardiac hypertrophy induced by angio-tensin-Ⅱ(Ang-Ⅱ)and its potential mechanism.Methods The rat cardiomyocyte cell line(H9C2)was cultured in vitro,and H9C2 cells were treated with Ang-Ⅱ to construct the myocardiac hypertrophy cell model induced by Ang-Ⅱ.H9C2 cells were treated with NRG-1,and mitochondrial membrane potential was detected by measuring myocardial cell surface area and reactive oxygen species(ROS)content.The protein expression of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),brain natriuretic peptide(BNP),silent information regulator 1(SIRT1),superoxide dismutase 1(SOD1)and NADPH oxidase isoform 2(NOX2)were detected by Western blot,and to observe the protective effect of NRG-1.Results Compared with the model group,NRG-1 was able to signifi-cantly decreased the cardiomyocytes surface area(P＜0.05),decreased the expression of hypertrophy markers ANP and BNP(P＜0.05)and the level of ROS(P＜0.05),increase the mitochondrial membrane potential(P＜0.05)and the expression of SOD1 and SIRT1(P＜0.05),and decreased the NOX2 protein levels(P＜0.05).The SIRT1 inhibitor EX527 blocked the protective effect of NRG-1.Conclusion NRG-1 ameliorates Ang-Ⅱ induced cardiomyocyte hypertrophy,and the underlying mechanism may be related to the SIRT1-NOX2 oxidative stress pathway.
NRG-1Ang-ⅡMyocardial hypertrophySilent information regulator 1Oxidative stress
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