利拉鲁肽通过NRF2改善高糖诱导的内皮细胞损伤

Liraglutide ameliorates high glucose⁃induced endothelial cell injuryvia Nrf2

目的探讨利拉鲁肽对高糖诱导的血管内皮细胞损伤的作用及机制。方法培养脐静脉内皮细胞(HUVECs),将细胞分为4组:对照组、高糖刺激组(HG组)、利拉鲁肽组、利拉鲁肽+HG组。采用ELISA法检测各组炎症细胞因子的分泌,采用试剂盒检测细胞内活性氧(ROS)的水平;采用试剂盒检测各组超氧化物歧化酶2(SOD2)和Gpx4的活性以及丙二醛(MDA)的水平;采用试剂盒检测一氧化氮(NO)含量;采用免疫印迹和免疫荧光染色法检测NRF2的核转位情况。结果HG组细胞肿瘤坏死因子⁃α(TNF⁃α)、白细胞介素(IL-1)和IL-6的水平相比对照组升高;细胞内ROS的水平增加,MDA水平增加,SOD2和Gpx4的活性减少;NO的含量减少;NRF2的核转位也明显减少。与HG组的细胞相比,利拉鲁肽+HG组细胞TNF⁃α、IL-1、IL-6的水平降低,细胞内的ROS水平降低,MDA水平降低,SOD2和Gpx4的活性增加;NO的含量增加;NRF2的核转位也明显增加。结论利拉鲁肽通过增加NRF2的核转位抑制高糖诱导的内皮细胞损伤。

Objective This study aimed to investigate the effect and mechanism of Liraglutide on high glucose-induced vascular endothelial cell injury.Methods Human umbilical vein endothelial cells(HUVECs)were cultured and divided into 4 groups:control,high glucose stimulation(HG),Liraglutide,and Liraglutide+HG group.ELISA was used to detect the secretion of inflammatory cytokines in each group,kits the levels of intracellular reactive oxygen species(ROS),the activity of SOD2 and Gpx4,and the level of MDA,and Western blot and immun of luorescence method nuclear translocation of Nrf2.Results The HG groupexhibited a significantly higher levels of tumor necrosis factor(TNF⁃α),interleukin(IL-1),IL-6,as well as the levels of intracellular ROS and MDA,but less activity of SOD2 and Gpx4,less contents of NO,and less nuclear translocation of Nrf2,as compared with the control group.Compared with the HG group,the Liraglutide+HG grouppresented significantly higher levels of TNF⁃α,IL-1,and IL-6,but lower levels of intracellular ROS and MDA,less activities of SOD2 and Gpx4,less contents of NO and less nuclear translocation of Nrf2.Conclusion Liraglutide suppresses high glucose-induced endothelial cell injury by increasing the nuclear translocation of Nrf2.