吡格列酮调控lncRNA GAS5/JNK信号通路对高糖诱导的胰岛β细胞损伤的影响  

Effect of pioglitazone on the regulation of lncRNA GAS5/JNK signaling pathway on hyperglycemic induced islet cell damage

作　　者：乌日娜[1] 丁海东[1] WU Rina;DING Haidong(Department of Endocrinology,Affiliated Hospital of Inner Mongolia University for nationalities,Tongliao 028000,China)

机构地区：[1]内蒙古民族大学附属医院内分泌科,内蒙古通辽028000

出　　处：《沈阳药科大学学报》2022年第8期957-962,共6页Journal of Shenyang Pharmaceutical University

摘　　要：目的 探讨吡格列酮是否通过调控lncRNA GAS5/JNK信号通路表达,影响高糖诱导的胰岛β细胞MIN6的凋亡、存活和胰岛素分泌。方法 体外培养胰岛β细胞MIN6,转染小干扰RNA(siRNA)阴性对照和lncRNA GAS5 siRNA,将细胞分为5组:对照组;高糖组;高糖+吡格列酮组;高糖+吡格列酮+si-NC组;高糖+吡格列酮+si-lncRNA GAS5组。采用流式细胞仪检测细胞凋亡情况,CCK8实验检测细胞存活,ELISA法检测细胞胰岛素分泌情况,Western blot实验检测凋亡相关蛋白Cleaved-caspase3和JNK通路蛋白表达,qRT-PCR检测lncRNA GAS5表达。结果 与对照组比较,高糖组MIN6细胞凋亡率和Cleaved-caspase3蛋白表达均明显升高,细胞存活率明显降低,细胞培养液中胰岛素含量明显减少,细胞中lncRNA GAS5表达明显减少,p-JNK蛋白表达明显升高;与高糖组比较,高糖+吡格列酮组MIN6细胞凋亡率和Cleaved-caspase3蛋白表达均明显降低,细胞存活率明显升高,细胞培养液中胰岛素含量明显增多,细胞中lncRNA GAS5表达明显升高,p-JNK蛋白表达明显降低;与高糖+吡格列酮+si-NC组比较,高糖+吡格列酮+si-lncRNA GAS5组MIN6细胞凋亡率和Cleaved-caspase3蛋白表达均明显升高,细胞存活率明显降低,细胞培养液中胰岛素含量明显减少,p-JNK蛋白表达明显升高。结论 吡格列酮对高糖诱导的胰岛β细胞MIN6损伤具有一定保护作用,其作用机制与上调lncRNA GAS5,抑制JNK信号通路活性有关。Objective To investigate whether pioglitazone affects the apoptosis, survival and insulin secretion of pancreatic cells MIN6 induced by high glucose by regulating the expression of lncRNA GAS5/JNK signaling pathway.Methods Islet cells MIN6 were cultured in vitro, transfected with small interfering RNA(siRNA) negative control and lncRNA GAS5 siRNA,and the cells were divided into 5 groups: control group;High glucose group;High glucose + pioglitazone group;High glucose + pioglitazone + si-NC group;High glucose + pioglitazone + si-lncRNA GAS5 group.Cell apoptosis was detected by flow cytometry, cell survival was detected by CCK8 assay, insulin secretion was detected by ELISA,expression of apoptosis-related proteins Cleaved caspase-3 and JNK pathways was detected by Western blot assay, and expression of lncRNA GAS5 was detected by qRT-PCR.Results Compared with the control group, cell apoptosis rate and Cleaved caspase-3 protein expression in the high-glucose group were significantly increased, cell survival rate was significantly reduced, insulin content in cell culture medium was significantly reduced, lncRNA GAS5 expression was significantly decreased, and p-JNK protein expression was significantly increased.Compared with the high-glucose group, the MIN6 cell apoptosis rate and Cleaved caspase-3 protein expression in the high-glucose + pioglitazone group were significantly reduced, cell survival rate was significantly increased, insulin content in cell culture medium was significantly increased, lncRNA GAS5 expression was significantly increased, and p-JNK protein expression was significantly decreased.Compared with the high-glucose + pioglitazone + si-NC group, the apoptosis rate of MIN6 cells and Cleaved caspase-3 protein expression in the high-glucose + pioglitazone + si-lncRNA GAS5 group were significantly increased, cell survival rate was significantly reduced, insulin content in cell culture was significantly reduced, and p-JNK protein expression was significantly increased.Conclusion Pioglitazone has a certai

关 键 词：吡格列酮 高糖 胰岛Β细胞 长链非编码RNA GAS5 JNK信号通路 

分 类 号：R917[医药卫生—药物分析学]