MEK1/2抑制剂PD98059对ox-LDL诱导HUVEC损伤的保护机制及对LOX-1表达影响

摘要

Objective To investigate the protective mechanism of MEK1/2 inhibitor PD98059 on ox-LDL induced injury of human umbilical vein endothelial cells (HUVEC),and its influence on the expression of LOX-1.Methods HUVEC damage models were established by using ox-LDL and were treated with PD98059 later,divided into the negative control group,the ox-LDL group,the positive control group and the PD98059+ox-LDL group.The effect of inhibition of MEK1/2 on ox-LDL induced HUVEC damage was measured.Results Compared with the negative control group,the levels in the ox-LDL group of LOX-1,pMEK1/2,RhoA,ROCK1,ROCK2,TNF-α and IL-6 were increased significantly,the proliferations of HUVEC and the productions of NO were decreased (P＜0.05).Compared with the ox-LDL group,the levels in the positive control group and the PD98059+ox-LDL group of pMEK1/2,RhoA,ROCK1,ROCK2,TNF-α and IL-6 were decreased,the proliferation of HUVEC and the production of NO were increased (P＜0.05).Conclusion PD98059 inhibit the MEK1/2 signaling pathway to suppress the ox-LDL induced damage of HUVEC by decreasing the expression of LOX-1.%目的 探讨MEK1/2抑制剂PD98059对氧化型低密度脂蛋白(ox-LDL)诱导人脐静脉内皮细胞(HUVEC)损伤的保护机制及对低密度脂蛋白受体-1(LOX-1)表达的影响.方法 使用ox-LDL诱导HUVEC损伤模型并进行PD98059处理,分阴性对照组、ox-LDL组、阳性对照组和PD98059+OX-LDL组;检测抑制MEK1/2对ox-LDL诱导HUVEC损伤的影响.结果 与阴性对照组比较,ox-LDL组LOX-1、pMEK1/2、RhoA、ROCK1、ROCK2、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的释放增多,细胞增殖能力及培养液中一氧化氮(NO)水平降低(P＜0.05);与ox-LDL组比较,阳性对照组和PD98059+ox-LDL组LOX-1、pMEK1/2、RhoA、ROCK1、ROCK2、TNF-α和IL-6的释放减少,细胞增殖能力及NO水平增高(P＜0.05).结论 PD98059抑制MEK1/2信号通路可降低HUVEC中LOX-1的表达以减轻ox-LDL诱导的内皮细胞损伤.