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目的探讨硫辛酸对胰岛素抵抗HepG2细胞内质网应激和超微结构改变的影响及机制。方法用高浓度胰岛素诱导胰岛素抵抗的细胞模型,用硫辛酸进行预处理,观察X盒结合蛋白-1(XBP-1)、氧调节蛋白150(ORP150)和细胞信号抑制因子-3(SOCS-3)mRNA表达的改变和用透射式电镜观察内质网超微结构的改变,流式细胞术检测细胞活性氧含量。结果硫辛酸预处理后XBP-1和ORP150 mRNA表达较对照组显著增强(P<0.05),而较胰岛素显著下降(P<0.05),SOCS-3 mRNA表达较对照组和胰岛素组显著减弱(P<0.05);细胞内质网损伤较胰岛素组明显减轻,硫辛酸预处理后细胞活性氧含量较胰岛素组明显下降(P<0.05)。结论硫辛酸对高浓度胰岛素诱导的HepG2细胞内质网应激有保护作用,其机制可能与其抗氧化作用和引起胰岛素抵抗相关的内质网应激蛋白的表达改变有关。
Objective To investigate the effect and mechanism of lipoic acid on the changes of endoplasmic reticulum stress and ultrastructure in insulin resistance HepG2 cells. Methods The cell model of insulin resistance induced by high concentration insulin was pretreated with lipoic acid. The expression of XBP-1, ORP150 and SOCS-3 ) mRNA expression changes were observed by transmission electron microscopy endoplasmic reticulum ultrastructure changes, flow cytometry detection of reactive oxygen species. Results Compared with the control group, the mRNA expression of XBP-1 and ORP150 in lipoic acid pretreated group was significantly increased (P <0.05), but decreased significantly compared with that in the control group (P <0.05). The expression of SOCS-3 mRNA was significantly decreased <0.05). Compared with the insulin group, the injury of endoplasmic reticulum (ER) was significantly reduced. The content of reactive oxygen species in lipoic acid pretreatment group was significantly lower than that in insulin group (P <0.05). Conclusion Lipoic acid has a protective effect on endoplasmic reticulum stress induced by high concentration of insulin in HepG2 cells. The mechanism may be related to the anti-oxidative effect and the expression of ER stress-related endoplasmic reticulum stress protein.