α-硫辛酸抑制糖基化终末产物诱导血管内皮细胞凋亡的研究

目的研究α-硫辛(ALA)对晚期糖基化终末产物(AGEs)诱导血管内皮细胞凋亡的抑制作用及机制。方法体外培养人脐静脉内皮细胞,加不同培养液孵育60 min,以人血清白蛋白(HSA)培养液作为对照组,以AGEs-HSA 200 mg/L培养液体外培养60 min为AGEs-HSA组,以ALA 200 μg/ml加入200 mg/L AGEs为ALA组,采用Hoechst 33258染色检测细胞凋亡,Western blot法检测NF-κB p65核蛋白表达,ELISA法测定天冬氨酸蛋白酶3(caspase-3)活性。结果 AGEs以浓度依赖方式促进内皮细胞凋亡。与对照组比较,AGEs-HSA组细胞NF-κB p65蛋白表达量明显减低,caspase-3活性明显增高(P0.05);与AGEs HSA组比较,ALA组内皮细胞凋亡明显减少,NF-κB p65蛋白表达量明显增加,caspase-3活性明显降低(P0.05)。结论 ALA可能通过增加NF-κB表达,抑制caspase-3激活的AGEs诱导内皮细胞凋亡。

Inhibitory effect of α-lipoic acid on vascular endothelial cell apoptosis induced by advanced glycosylation end products

Objective To investigate the inhibitory effect of a-lipoic acid (ALA) on vascular endothelial cell apoptosis induced by advanced glycosylation end products(AGEs) and possible mechanism. Methods HUVECs were cultured in vitro and treated with different concentrations of AGEs and ALA.The cell morphology was observed after Hoechst 33258 staining.The change of NF-κB p65 protein was assessed by Western blot analysis and the caspase-3 activity was detected by ELISA.Results Morphological observation indicated that AGEs induced characteristic apoptotic changes in HUVECs in a dose-dependent manner.AGEs decreased the expression of NF-κB p65 protein and increased the caspase-3 activity as compared with the controls.ALA decreased the endothelial cell apoptosis,increased the expression of NF-kB p65 protein and decreased the caspase -3 activity as compared with the control.Conclusion AGEs can induce the apoptosis of vascular endothelial cells in vitro.ALA effectively inhibits AGEs-induced apoptosis by increasing the expression of NF-kB p65 protein and decreasing the caspase-3 activity in endothelial cells.