激活 TGR5通过 CaN／NFAT3途径减轻高糖诱导的心肌细胞肥大

摘要

AIM: To investigate the role of G-protein-coupled bile acid receptor 1 ( GPBR1; also known as TGR5) activation in high glucose-induced cardiomyocyte hypertrophy and calcineurin (CaN)/nuclear factor of activated T-cells 3 (NFAT3) signaling.METHODS:Primarily cultured mouse cardiomyocytes were used in the study .The cell surface areas of the cardiomyocytes were measured by an image analysis system .The cell protein content was detected by BCA meth-od.The expression of TGR5, CaN and NFAT3 at mRNA and protein levels was determined by RT-PCR and Western blot . RESULTS:The mouse cardiomyocytes were successfully cultured .High glucose significantly induced the increases in the cell surface area, the cell protein content and the expression of CaN and NFAT 3 (P<0.05) in the cardiomyocytes.TGR5 activation or a CaN antagonist cyclosporin A inhibited high glucose-induced cardiomyocyte hypertrophy and the expression of CaN and NFAT3 (P<0.05).These effects of TGR5 activation were abolished by TGR5 gene interference (P<0.05). CONCLUSION:TGR5 activation reduces high glucose-induced cardiomyocyte hypertrophy by inhibiting CaN /NFAT3 sig-naling.%目的：观察激活G蛋白偶联胆汁酸受体1（GPBAR1，又称TGR5）对高糖诱导的小鼠心肌肥大的影响，并探讨钙调神经磷酸酶（CaN）／活化T细胞核因子3（NFAT3）信号途径在其中的作用。方法：原代培养小鼠心肌细胞，采用图像分析系统测定细胞表面积， BCA 法测定细胞蛋白含量，通过RT-PCR及Western blot 方法检测TGR5、CaN及NFAT3的mRNA及蛋白表达变化。结果：成功培养小鼠心肌细胞。高糖明显诱导心肌细胞表面积及细胞蛋白含量的增加（P＜0.05），同时CaN及NFAT3的表达也增加（P＜0.05）。激活TGR5或给予CaN抑制剂环孢素A均能抑制高糖引起的心肌细胞肥大及NFAT3表达增加（P＜0.05）。给予TGR5干扰慢病毒可阻断TGR5对心肌细胞肥大的上述改善作用（ P＜0.05）。结论：激活TGR5能减轻高糖诱导的心肌细胞肥大，其机制可能与抑制CaN／NFAT3信号通路有关。