G蛋白信号调节因子6对心肌细胞肥大的作用及机制研究  

Role and molecular mechanism of RGS6 in regulation of cardiomyocyte hypertrophy

作　　者：舒婧娴 陆瑶[1] 蔡菁菁[3] 鄢光宇 陈子莹 刘媛媛 袁洪[1] SHU Jing-xian;LU Yao;CAI Jing-jing;YAN Guang-yu;CHEN Zi-ying;LIU Yuan-yuan;YUAN Hong(Center of Clinical Pharmacology, the 3rd Xiangya Hospital of Central South University, Changsha 410013,China;Dept of Pharmacy, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai Guangdong 519000, China;Dept of Cardiology, the 3rd Xiangya Hospital of Central South University, Changsha 410013, China)

机构地区：[1]中南大学湘雅三医院临床药理中心,湖南长沙410013 [2]中山大学附属第五医院药学部,广东珠海519000 [3]中南大学湘雅三医院心内科,湖南长沙410013

出　　处：《中国药理学通报》2020年第4期519-526,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81770403);广东省医院药学研究基金资助项目(No 2019YX18)。

摘　　要：目的探讨G蛋白信号调节因子6(RGS6)对心肌细胞肥大的调控作用及机制。方法用AdRGS6和AdshRGS6慢病毒分别感染心肌细胞使RGS6表达上下调,AngⅡ构建肥大模型。测定各组细胞面积和ANP、BNP的表达,检测活性氧(ROS)和丝裂原活化蛋白激酶(ERK1/2、p38、JNK1/2)的表达。明确改变的信号通路后,用ROS抑制剂(DPI)开展逆转实验。结果 (1)与AdG FP/AngⅡ组相比,AdRGS6/AngⅡ组细胞面积、ANP和BNP明显增加,信号通路中ROS和磷酸化(p)-JNK1/2表达增加。(2)与AdshRNA/AngⅡ相比,AdshRGS6/AngⅡ组细胞面积、ANP和BNP明显降低,信号通路中ROS和p-JNK1/2表达下降。(3)逆转实验:与AdRGS6/AngⅡ组相比,DPI干预的AdRGS6/AngⅡ组心肌细胞面积明显降低,p-JNK1/2蛋白表达降低。结论 RGS6通过激活ROS/JNK1/2通路促进心肌细胞肥大。Aim To explore the regulatory effect and mechanism of Regulators of G-protein Signaling 6(RGS6)in AngⅡ-induced hypertrophy.Methods RGS6 expression was up-and down-regulated respectively by AdRGS6 and AdshRGS6 lentivirus.Each group was treated with AngⅡ/PBS.Cell size and changes of hypertrophic markers(ANP and BNP)were evaluated.Then ROS levels and the total protein and phosphorylated protein of ERK1/2,p38,JNK1/2 in each group were detected.When the altered signaling was clarified,a reversal experiment of hypertrophic cardiomyocytes was conducted to further verify the signaling pathway.The RGS6 up-regulated cardiomyocytes of hypertrophy treated with ROS inhibitor(DPI)were experimental group.Results①After stimulated with AngⅡfor 48 h,the size of AdRGS6-infected cell increased compared with AdGFP infection group.In addition,the mRNA levels of ANP and BNP also increased.After stimulated with AngⅡ,the ROS levels and p-JNK1/2 proteins of AdRGS6-infected cells all increased compared with AdGFP infection group.②After stimulated with AngⅡfor 48h,the size of AdshRGS6-infected cell decreased compared with AdshRNA infection group and the mRNA levels of ANP and BNP also decreased.The ROS levels and p-JNK1/2 proteins of AdshRGS6-infected cell all decreased compared with AdshRNA infection group.③In the reversal experiments,compared with AdRGS6+AngⅡ/DMSO group,the size of AdRGS6+AngⅡ/DPI cardiomyocytes significantly decreased,and the downstream signaling of p-JNK1/2 was improved.Conclusions RGS6 may be a key factor to cardiac hypertrophy.RGS6 aggravates AngⅡ-induced cardiomyocyte hypertrophy via activating ROS-KNK1/2 signaling pathway.

关 键 词：G蛋白信号调节因子6(RGS6) 心肌细胞肥大 血管紧张素Ⅱ(AngⅡ) 机制 ROS/JNK1/2信号通路 丝裂原活化蛋白激酶(MAPK) 

分 类 号：R-332[医药卫生] R322.11