阿托伐他汀对高糖诱导的人脐静脉内皮细胞氧化应激损伤的作用及其机制

目的 探讨阿托伐他汀（atorvastatin,Atv）对高糖环境下人脐静脉内皮细胞氧化应激损伤的作用及其可能的机制.方法 人脐静脉内皮细胞株低糖（5.6 mmol/L）培养贴壁后随机分为正常组（NG）、渗透压对照组（OS）、高糖组（HG）、高糖＋不同浓度药物组（HG＋0.1、1.0、10.0 μmol/L Atv）,药物培养24 h后应用CCK-8法检测细胞增殖情况,流式细胞仪检测细胞内活性氧（ROS）的水平,Western blot法检测细胞中SIRT1蛋白表达水平.结果 与正常组相比,高糖组细胞增殖减少,药物干预可改善高糖对人脐静脉内皮细胞增殖的抑制作用,呈浓度依赖性.高糖环境下,细胞内ROS生成显著增加,SIRT1蛋白表达明显降低.阿托伐他汀可以上调高糖环境下SIRT1的表达水平,降低高糖诱导的ROS的表达增加水平,具有浓度依赖性.结论 阿托伐他汀可以对抗高糖诱导的人脐静脉内皮细胞的氧化损伤,其可能的机制与升高内皮细胞SIRT1的表达有关.

Effects of atorvastatin on high glucose-induced oxidative damage in human umbilical vein endothelial cells and its mechanism

Objective To explore the effects of atorvastatin on high glucose - induced oxidative damage in human umbilical vein endothelial cells and its underlying mechanism. Methods Human umbilical vein endothelial cells were cultured in low - glucose medium （ 5.6 mmol/L） and then divided to appropriate experimental groups ： a normal glucose （NG） group, an osmotic pressure control group （OS, 5.6 mmol/L glucose ＋ 27.7 mmol/L mannitol） , a high glucose group （ HG, 33.3 mmol/L） , various concentrations of atorvastatin groups （ HG ＋ Atv, 0. 1, 1.0 and 10.0 μmol/L）. After 24 hours of incubation, the proliferative rate of the cells was tested by CCK - 8 method. The level of ROS was de- tected by flow cytometry. The expression of SIRT1 was observed using western blotting. Results Compared with normal cells, the cells exposed to high glucose presented a reduced proliferative rate, which could be reversed by atorvastatin treatment in a concentration dependent way. High glucose remarkably stimulated the production of ROS hut reduced the amount of SIRT1, which were attenuated after exposure to Atv in a concentration dependent manner. Conclusion Atorv- astatin treatment can resist the oxidative stress induced by high glucose in human umbilical vein endothelial cells, which may attribute to enhanced expression of SIRT1.