Cortactin/N-cadherin信号轴在病理性心肌肥大中的作用  

Function of Cortactin/N-cadherin signal axis in pathological myocardial hypertrophy

作　　者：王钺镁 喻文静 孙袭孟 张静 路静 刘培庆[1] WANG Yue-mei;YU Wen-jing;SUN Xi-meng;ZHANG Jing;LU Jing;LIU Pei-qing(School of Pharmaceutical Science,Sun Yat-Sun University,Guangzhou 510006,China)

机构地区：[1]中山大学药学院,广东广州510006

出　　处：《中国药理学通报》2024年第2期234-242,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82173808,U21A20419);广东省自然科学基金资助项目(No 2021B1515020100)。

摘　　要：目的探究皮层肌动蛋白结合蛋白(Cortactin)对异丙肾上腺素(isoprenaline,ISO)诱导的病理性心肌肥大的调控作用及其机制。方法采用ISO刺激新生大鼠心肌细胞(neonatal rat cardiomyocytes,NRCMs)24 h,在细胞水平建立心肌肥大模型;C57BL/6小鼠皮下注射ISO 1周,在动物水平建立心肌肥大模型。采用RT-qPCR检测mRNA的变化;免疫印迹法检测相应蛋白含量的变化;免疫荧光法检测Cortactin的亚细胞定位及表达量的变化;采用腺病毒感染的方法过表达Cortactin,通过转染小干扰RNA敲低Cortactin。结果在细胞和动物水平上,成功建立ISO诱导的心肌肥大模型,均观察到ISO引起Cortactin和N型钙黏连蛋白(N-cadherin)水平降低;过表达Cortactin可逆转ISO导致的N-cadherin蛋白水平的降低及心肌细胞肥大反应;敲低Cortactin则显示相反的效应。结论Cortactin可能联合N-cadherin通过增强心肌细胞之间的连接,发挥抗心肌肥大的作用。Aim To investigate the regulatory effect of Cortactin on pathological myocardial hypertrophy induced by isoprenaline(ISO)and the underlying mechanism.Methods ISO was used to stimulate neonatal rat cardiomyocytes for 24 h,and myocardial hypertrophy model was established at the cellular level.C57BL/6 mice were injected subcutaneously with ISO for one week to establish myocardial hypertrophy model at animal level.RT-qPCR was used to detect the changes of mRNA and Western blot was used to detect the changes of relative protein content.Immunofluorescence was used to measure the subcellular location of Cortactin and the change of its expression.The overexpression of Cortactin by adenovirus infection and the knockdown of Cortactin by transfection of small interfering RNA were studied.Results On the cellular and animal levels,ISO-induced myocardial hypertrophy models were successfully established,and it was observed that ISO caused the decrease of Cortactin and N-cadherin protein levels.Overexpression of Cortactin could reverse the decrease of N-cadherin protein level and myocardial hypertrophy caused by ISO.Knockdown of Cortactin showed the opposite effect.Conclusion Cortactin,in combination with N-cadherin,may play a role in combating myocardial hypertrophy by enhancing the connections between cardiomyocytes.

关 键 词：异丙肾上腺素 心肌肥大 心肌细胞 肌动蛋白结合蛋白 N-CADHERIN 细胞连接 

分 类 号：R-332[医药卫生] R329.24R329.411R542.2R971.93