Protective Effect of Alpha-lipoic Acid on INS-1 Cells of Rats Cultured with High Glucose

目的 观察α-硫辛酸对高糖环境下INS-1细胞的抗氧化作用及对胰岛素分泌的影响,探讨α-硫辛酸对胰岛β细胞的保护作用.方法 INS-1细胞分为3组:对照组(11.1 mmol/L葡萄糖处理)、高糖组(30 mmol/L葡萄糖处理)和观察组(30 mmol/L葡萄糖+200 μmol/L α-硫辛酸处理).分组培养48 h后检测活性氧生成的情况,行葡萄糖刺激胰岛素分泌试验(GSIS)测定胰岛素含量,测定各组氧化应激相关指标,测定核因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)、醌氧化还原酶l(NQO1) mRNA表达情况.结果 高糖组细胞存活率、超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶1(GPX-1)和过氧化氢酶(CAT)含量低于对照组(P＜0.05),活性氧和丙二醛含量高于对照组(P＜0.05).观察组细胞存活率、SOD、GPX-1和CAT含量高于高糖组(P＜0.05),活性氧和丙二醛含量低于高糖组(P＜0.05).高糖组基础胰岛素分泌和GSIS试验胰岛素分泌量以及SOD、GPX-1、CAT、HO-1和NQ01 mRNA表达低于对照组(P＜0.05).观察组基础胰岛素分泌和GSIS试验胰岛素分泌量以及SOD、GPX-1、CAT、Nrf2、HO-1和NQO1mRNA表达高于高糖组(P＜0.05).结论 α-硫辛酸显著降低胰岛β细胞在高糖环境下的氧化损伤,增强胰岛β细胞GSIS的功能,对胰岛β细胞具有保护作用.Objective To observe effects of α-lipoic acid on anti-oxidation of INS-1 cells and insulin secretion under high glucose environment,and to investigate protective effect of α-lipoic acid on pancreatic β cells.Methods INS-1 cells were divided into control group (11.1 mmol/L glucose treatment),high glucose group (30 mmol/L glucose treatment) and observation group (30 mmol/L glucose + 200 μmol/L α-lipoic acid treatment).After 48 h of cultivation,production conditions of reactive oxygen were detected,glucose-stimulated insulin secretion (GSIS) assay was performed to detect insulin concentration.Related indexes of oxidative stress,and mRNA expressions of nuclear factor E2-related factor 2 (Nrf2),heme oxygenase-1 (HO-1),NAD(P) H quinone oxidoreductase (NQO1) were also detected.Results In high glucose group,values of cell survival rate,and contents of superoxide dismutase (SOD),glutathione peroxidase 1 (GPX-1) and catalase (CAT) were significantly lower (P ＜ 0.05),while reactive oxygen species and malondialdehyde contents were significantly higher than those in control group (P ＜ 0.05).In observation group,values of cell survival rate,SOD,GPX-1 and CAT contents were significantly higher (P ＜ 0.05),while reactive oxygen species and malondialdehyde contents were significantly lower than those in high glucose group (P ＜ 0.05).Values of basal insulin secretion,insulin secretion in GSIS assay,and mRNA expressions of SOD,GPX-1,CAT,HO-1 and NQO1 in high glucose group were significantly lower than those in control group (P ＜ 0.05).Values of basal insulin secretion,insulin secretion in GSIS assay,and mRNA expressions of SOD,GPX-1,CAT,Nrf2,HO-1 and NQO1 in observation group were significantly higher than those in high glucose group(P ＜ 0.05).Conclusion The α-lipoic acid can significantly reduce oxidative damage of islet β cells under high glucose environment and enhance GSIS function of pancreatic β cells,and it has protective effect on pancreatic β cells.国家自然科学基金项目61-52