西南医科大学学报2024，Vol.47Issue(6)：528-534,7.DOI:10.3969/j.issn.2096-3351.2024.06.012
G蛋白偶联胆汁酸受体1通过抑制内质网应激减轻内皮素-1介导的乳鼠心肌细胞凋亡
G protein-coupled bile acid receptor 1 reduces endothelin-1-mediated apopto-sis in murine cardiac myocytes by inhibiting endoplasmic reticulum stress
摘要
Abstract
Objective The purpose of this study was to observe the effects of the activation of G protein-coupled bile acid receptor 1(TGR5)on endothelin-1(ET-1)-mediated apoptosis in cardiac muscle cells and to explore its underlying mechanisms.Methods Initially,the study was divided into a control group and an ET-1 group.ET-1 concentrations were set at 10-6,10-7 and 10-8 mmol/L,and cells were cultured for 12,24,36 and 48 hours,respectively.Flow cytometry was used to measure the apoptosis rate at different time points for each group.The concentration and time of ET-1 with higher apoptosis rate were selected for subsequent experiments.Follow-up experiments included the control group,ET-1 group,TGR5 agonist group,TGR5 expression inhibition group,and TGR5 empty virus group.Flow cytometry was used to detect the apoptosis rate of cardiomyocytes in each group,CCK8 was used to measure the survival rate of cardiomyocytes,and RT-PCR was used to detect TGR5 mRNA.Western blot detection of TGR5,C/EBP homologous protein(CHOP),C-jun-n-terminal protein kinase(JNK),phosphorylated JNK(p-JNK),and aspartate-specific cysteine protease(Casepase-12).Results ET-1 induced cardiomyocyte apoptosis in a concentration-dependent manner within the range of 10-8-10-6 mmol/L and in a time-dependent manner within 48 h(P＜0.05).Subsequent experiments showed that after activation of TGR5,compared with the ET-1 group,the apoptosis rate of cardiomyocytes was decreased,the survival rate of cardiomyocytes was increased,and the expression of CHOP,p-JNK,and Caspase12 protein was inhibited(P＜0.05).However,inhibition of TGR5 expression could block the inhibitory effect of TGR5 on apoptosis of cardiomyocytes,reduce the survival rate of cardiomyocytes,and increase the expres-sion of CHOP,p-JNK,and Caspase12 proteins(P＜0.05).Conclusion ET-1 could induce myocardial cell apoptosis in suckling mice.Mechanisms may be related to endoplasmic reticulum stress(ERS)hyperactivation.TGR5 might antagonize the apoptosis-promoting effect of ET-1 on cardiomyocytes by inhibiting ERS.关键词
G蛋白偶联胆汁酸受体1/心肌细胞凋亡/内皮素-1/内质网应激Key words
G protein-coupled bile acid receptor 1/Myocardial apoptosis/Endothelin-1/Endoplasmic reticulum stress分类
临床医学引用本文复制引用
陈德秀,雷贤英,李家富..G蛋白偶联胆汁酸受体1通过抑制内质网应激减轻内皮素-1介导的乳鼠心肌细胞凋亡[J].西南医科大学学报,2024,47(6):528-534,7.基金项目
西南医科大学科技项目资助(2021ZKQN092) （2021ZKQN092）
