过氧化氢诱导胰岛β细胞凋亡及TIMP-1的保护作用

Protective effects of Tissue inhibitor of metalloproteinase-1 on apoptosis of insulin-producing RINm5F cells induced by hydrogen peroxide

目的:研究过氧化氢诱导的胰岛β细胞凋亡及基质金属蛋白酶抑制剂-1(TIMP-1)的保护作用和可能机制。方法:过氧化氢诱导大鼠胰岛瘤细胞RINm5F细胞凋亡,实验组予以TIMP-1干预。应用MTT法和Caspase-3活性检测来比较各组间细胞活力和Caspase-3活性的差异,检测超氧化物歧化酶(SOD)活性来反映各组之间抗氧化能力的差异。结果:应用0.1mmol/L过氧化氢干预1h,能明显诱导RINm5F细胞凋亡,过氧化氢刺激前TIMP-1(50μg/L)预处理1h较单独过氧化氢刺激组细胞活力上升约35%,Caspase-3活性下降约21%,SOD活性增加约46%,两组比较差异有显著性意义(P<0.05)。结论:TIMP-1对过氧化氢诱导的RINm5F细胞的凋亡有保护作用,其机制可能是通过诱导SOD酶的活性增加来实现的。

Objective：To investigate the effect of tissue inhibitor of metalloproteinase-1 （TIMP-1） on the apoptosis of β cell induced by hydrogen peroxide and the mechanism of TIMP-1 action. Methods：The insulin-producing rat cell line RINm5F cells were cultured and stimulated by H2O2 with or without the addition of TIMP-1 （50 μg/L）. Cell viability,Caspase-3 and superoxide dismutase （SOD） activity were determined after the cells were exposed to H202 and TIMP-1. Results：Cell viability was decreased obviously in RINm5F cells after incubation with H2O2（0.1 mmol/L） for 1 hour alone. In the cells after treatment with TIMP-1 （50 μg/L） for 1 hour prior to H2O2,cell viability and SOD activity were remarkably increased and the activity of Caspase-3 was lower significantly than that in the cells treated by H2O2 alone（P 〈 0.05 ）. Conclusion：TIMP-1 can protect RINm5F cells from apoptosis induced by hydrogen peroxide, which possibly involves in raising the activity of SOD.