G蛋白偶联胆汁酸受体1激活对高糖诱导小鼠心肌细胞肥大的影响  

Effect of G-protein-coupled bile acid receptor 1 activation on high glucose-induced cardiomyocyte hypertrophy in mice

作　　者：冯健 吴丹 陈旭昕[2] 刘应才 李家富 FENG Jian WU Dan CHEN Xuxin LIU Yingcai LI Jiafu(The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China)

机构地区：[1]西南医科大学附属医院,四川泸州646000 [2]中国人民解放军海军总医院

出　　处：《山东医药》2017年第1期1-3,共3页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(31300946)

摘　　要：目的探讨G蛋白偶联胆汁酸受体1(TGR5)激活对高糖诱导小鼠心肌细胞肥大的影响。方法原代培养小鼠心肌细胞,将细胞分为对照组、高糖组、高糖+INT-777(TGR5受体激动剂)组、高糖+INT-777+TGR5shRNA(以TGR5干扰慢病毒包装)组。采用图像分析系统测定各组细胞表面积,通过RT-PCR及Western blotting方法检测TGR5干扰慢病毒效率,RT-PCR检测各组促肥大因子(心房钠尿因子、β-肌球蛋白重链)mRNA表达变化。结果成功培养小鼠心肌细胞。与对照组比较,高糖组心肌细胞表面积及促肥大因子mRNA表达增加(P均<0.05)。激活TGR5后,由高糖导致的心肌细胞表面积及促肥大因子mRNA表达的增加受到抑制(P均<0.05)。与激活TGR5组比较,干扰TGR5基因后,心肌细胞表面积及促肥大因子mRNA表达明显增加(P均<0.05)。结论激活TGR5受体可以抑制高糖诱导的心肌细胞肥大及促肥大因子mRNA表达,可能是糖尿病性心肌病重要的药物治疗靶点。Objective To investigate the effect of G-protein-coupled bile acid receptor 1 （TGRS） receptor activation on high glucose-induced cardiomyocyte hypertrophy in mice. Methods After primary culture of mouse Cardiomyocytes, the cells were divided int0 the control＇group, high glucose group, high glucose ＋ INT-777 （ the agonist of TGR5 receptor） and high glucose ＋ INT-777 ＋ TGP,5 shRNA group. Image analysis system was used for determination of cell surface area, RT- PCR and Western blotting were used to detect the lentivirus efficiency of TGR5 interference, and the expression of pro-hy- pertrophy genes was detected by RT-PCR. Results The mouse cardiomyocytes were successfully cultured. Compared with the control group, cardiomyocytes＇ surface area and pro-hypertrophy gene mRNA expression increased in the high glucose group （ all P 〈 0.05 ）. TGR5 activation inhibited the increase of cardiomyocytes＇ surface area and pro-hypertrophy gene mRNA expression which was induced by high glucose （ all P 〈 0.05）. Compared with high glucose ＋ INT-777 group, car- diomyocytes＇ surface area and pro-hypertrophy gene mRNA expression increased significantly after TGR5 gene interference （all P 〈 0.05 ）. Conclusion TGR5 receptor, activation can inhibit cardiomyocyte hypertrophy and pro-hypertrophy gene mRNA expression induced by high glucose, which may be an important drug target for diabetic cardiomyopathy.

关 键 词：心肌细胞肥大 G蛋白偶联胆汁酸受体 高糖诱导 INT-777 心房钠尿因子 Β-肌球蛋白重链 小鼠 

分 类 号：R542.2[医药卫生—心血管疾病]