Apelin通过抑制高糖介导的氧化应激保护血管内皮功能

Apelin protects endothelial function via inhibiting high glucose-induced oxidative stress

目的探讨Apelin对高糖诱导的原代人脐静脉内皮细胞(HUVECs)中活性氧(ROS)生成和糖尿病(DM)小鼠内皮依赖性血管功能障碍的影响。方法 (1)体外实验采用高浓度葡萄糖培养基诱导HUVECs细胞损伤,Apelin-13预处理1h后测定细胞内Apelin-13、ROS水平和Caspase-3的活性(ELISA法测定)。(2)构建1型糖尿病小鼠模型,予Apelin-13干预后,血管张力仪测定主动脉环内皮依赖性血管舒张功能和非内皮依赖性血管舒张功能。结果与对照组相比,高糖诱导后的HUVECs内Apelin-13的含量明显下降(P=0.01);高糖诱导后HUVECs中ROS生成和Caspase-3的活性增加,而Apelin干预可显著降低高糖诱导的ROS生成和Caspase-3的活性(P=0.03,P=0.04)。此外,与对照组相比,DM小鼠主动脉环内皮依赖性血管舒张功能显著下降(P=0.02),而Apelin干预可有效地减轻DM小鼠血管内皮功能障碍。结论 Apelin抑制高糖诱导的血管内皮细胞活性氧生成和细胞凋亡,减轻DM小鼠血管内皮功能障碍。

Objective To investigate the role of Apelin in reactive oxygen species( ROS) production in primary human umbilical vein endothelial cells( HUVECs) and endothelium-dependent vascular dysfunction in diabetic mice.Methods(1)HUVECs were cultured by medium of high concentration of glucose to induce damage. After pretreatment of Apelin-13 for 1 h,the ROS production and Caspase-3 activity( ELISA) were detected respectively.(2)40 experimental type 1 diabetic mice were randomized equally into control group and diabetic group. Apelin-13 production,endotheliumdependent relaxation and endothelium-independent relaxation in aortic ring were determined respectively. Results Significant decreased Apelin-13 production was observed in HUVECs by high glucose compared with the control group( P = 0. 01)). Exposure to high glucose increased ROS production and Caspase-3 activity by HUVECs,which were significantly preserved by pretreatment of Apelin-13( P = 0. 03,P = 0. 04). Furthermore,in mouse models of STZ-induced type 1 diabetes,the endothelium-dependent relaxation in aortic ring reduced significantly( P = 0. 02),which was reversed by pretreatment with Apelin-13. Conclusions Apelin could inhibit vascular endothelial cell ROS generation and apoptosis induced by high glucose,and ameliorate the endothelial dysfunction in diabetic mice.