异钩藤碱抑制Akt通路减轻血管紧张素Ⅱ诱导的心肌细胞肥大  

Isorhynchophylline attenuates angiotensinⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt pathway

作　　者：谷玉雷[1,2,3] 刘怡 朱志强 裴辉[1,2,3] 姜毓敏 谢佳丰[1,2,3] 毛宇径 张晓凡 高路 肖莉丽 Gu Yulei;Liu Yi;Zhu Zhiqiang;Pei Hui;Jiang Yumin;Xie Jiafeng;Mao Yujing;Zhang Xiaofan;Gao Lu;Xiao Lili(Department of Emergency Medicine,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Henan Provincial Emergency and Trauma Engineering Research Center,Zhengzhou 450052,China;Henan Key Laboratory of Emergency Medicine and Trauma Research,Zhengzhou 450052,China;Department of Cardiology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院急诊医学科,郑州450052 [2]河南省急诊与创伤工程研究中心,郑州450052 [3]河南省急诊与创伤研究医学重点实验室,郑州450052 [4]郑州大学第一附属医院心血管内科,郑州450052

出　　处：《中华急诊医学杂志》2024年第5期665-670,共6页Chinese Journal of Emergency Medicine

基　　金：河南省医学科技攻关项目(SBGJ202103066);河南省高等学校重点项目(22A320052);河南省科技攻关项目(222102310505)。

摘　　要：目的研究异钩藤碱(isorhynchophylline,IRN)对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的心肌细胞肥大的作用及机制。方法H9c2细胞与AngⅡ、不同浓度的IRN(0、5、10、25、50μmol/L)共培养,检测细胞表面积及心肌肥大标志物心房利钠肽(atrial natriuretic peptide,ANP)、脑利钠肽(brain natriuretic peptide,BNP)、β-肌球蛋白重链(β-myosin heavy chain,β-MHC)mRNA水平来阐述IRN对心肌肥厚的作用及最有效浓度。H9c2细胞与AngⅡ和IRN(25μmol/L)在不同时间(0 h、6 h、12 h、24 h)共培养,研究抑制的最有效时间。检测信号通路的磷酸化水平,然后使用IRN和Akt抑制剂MK2206对信号通路磷酸化水平的影响来进一步研究潜在的作用机制。结果与control组相比,AngⅡ组H9c2细胞表面积显著增加(均P<0.05),心肌肥大标志物ANP、BNP和β-MHC mRNA表达显著增加(均P<0.05);不同浓度的IRN(5、10、25、50μmol/L)预处理均可抑制AngⅡ引起的细胞表面积增加(均P<0.05),尤其是在浓度为25μmol/L时(P<0.01);IRN可以时间依赖性的抑制AngⅡ诱导的ANP、BNP、β-MHC mRNA激活(均P<0.05)。AngⅡ引起Akt、GSK3β、mTOR、FOXO3a的磷酸化水平升高;IRN可以阻断AngⅡ诱导的Akt信号通路磷酸化。结论IRN通过抑制Akt信号通路减轻AngⅡ诱导的心肌细胞肥大。Objective To investigate the effect and mechanism of isorhynchophylline(IRN)on angiotensinⅡ(AngⅡ)-induced cardiac hypertrophy.Methods H9c2 cells were co-cultured with AngⅡand different concentrations of IRN(0,5,10,25,50μmol/L).The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)andβ-myosin heavy chain(β-MHC)were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration.H9c2 cells were co-cultured with AngⅡand IRN(25μmol/L)at different times(0,6,12,24 h)to elucidate the most effective time of inhibition.The phosphorylation levels of the signaling pathway were detected,and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results Compared with the control group,the surface area of H9c2 cells,and the mRNA expression of myocardial hypertrophy markers ANP,BNP andβ-MHC were significantly increased(all P<0.05).Pretreated with different concentrations of IRN(5,10,25,50μmol/L)could inhibit the increase in cell surface area induced by AngⅡ(all P<0.05),especially at the concentration of 25μmol/L(P<0.01).IRN could time-dependently inhibit AngⅡ-induced activation of ANP,BNP,β-MHC mRNA(all P<0.05).AngⅡcaused increased phosphorylation levels of Akt,GSK3β,mTOR and FOXO3a.IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway.Conclusion IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.

关 键 词：异钩藤碱 血管紧张素Ⅱ 心肌肥大 H9C2细胞 蛋白激酶B 

分 类 号：R285[医药卫生—中药学]