解放军医学杂志2018，Vol.43Issue(2)：101-106,6.DOI:10.11855/j.issn.0577-7402.2018.02.03
抑制G蛋白偶联受体35对小鼠缺血性心肌损伤的保护作用
Inhibition of GPR35 attenuates ischemic myocardial injury
摘要
Abstract
Objective To investigate the protective role of GPR35 inhibition on hypoxic myocardial cell line and mouse myocardial infarction (MI) model.Methods For investigating the changes of GPR35 expression in hypoxic environment,the murine myocardial cells (MCM) were divided into normoxia group and hypoxia group,the mRNA expression of GPR35 was determined by q-PCR and the protein level was measured by Western blotting 6h after incubation.For further studying the role of GPR35,MCM were divided into four groups:normoxia,hypoxia,hypoxia+vehicle,hypoxia+CID2745678 (GPR35 inhibitor,3μmol/L) group.Accordingly,the apoptosis of cardiomyocytes was measured by flow cytometer and TUNEL.For investigating the changes of GPR35 expression in the state of myocardial ischemia,the C57 male mice were divided into sham group (n=6) and MI group (n=8),the mRNA expression of GPR35 was determined by q-PCR and the protein level was measured by Western blotting 3 days after MI.For further studying the role of GPR35,the C57 mice were divided into four groups:sham (n=6),MI (n=8),MI+vehicle (n=8) and MI+CID2745678 (n=8) group.Ultrasound echocardiography was performed 4 weeks after MI.Mice were then sacrificed and the hearts were removed and stained with Masson to measure the myocardial fibrosis area.Results Compared with normoxia group,the levels of GPR35 mRNA and protein increased obviously in hypoxia group (P＜0.01,P＜0.05);Compared with hypoxia+vehicle group,the myocardial cells apoptosis in hypoxia+CID2745678 group decreased markedly (P＜0.05).Three days after MI,compared with the sham group,the levels of GPR35 mRNA and protein increased obviously (P＜0.01,P＜0.05) in MI group;Compared with MI+vehicle group,the left ventricular fraction shortening (LVFS) and left ventricular ejection fraction (LVEF) relieved obviously (P＜0.05) and myocardial fibrosis level declined markedly in MI+CID2745678 group (P＜0.05).Conclnsion Inhibition of GPR35 could decrease the apoptosis of cardiomyocytes cultured in hypoxia and attenuated the injury of myocardial ischemia.关键词
G蛋白偶联受体35/缺氧/缺血/细胞凋亡/心脏功能Key words
G protein-coupled receptors 35/hypoxia-ischemia/apoptosis/heart function分类
医药卫生引用本文复制引用
贺磊,杨怡,田玥,王挺,沈阳,裴海峰,杨大春..抑制G蛋白偶联受体35对小鼠缺血性心肌损伤的保护作用[J].解放军医学杂志,2018,43(2):101-106,6.基金项目
国家自然基金青年科学基金(81500208) （81500208）
四川省科技厅青年基金项目(2017JQ0012) （2017JQ0012）
中国博士后基金面上项目(2017M613429)This work was supported by the National Natural Science Foundation of China (81500208),the Science Fund for Distinguished Young Scholars of Sichuan Province (2017JQ0012),and the General Program of China Postdoctoral Foundation (2017M613429) （2017M613429）
