阿托伐他汀抑制TRPM2表达和开放对血管内皮氧化应激的影响

Effect of Atorvastatin Inhibiting TRPM2 Expression and Opening on Vascular Endothelial Oxidative Stress

为探讨阿托伐他汀对瞬时受体电位通道M2(TRPM2)表达和功能的影响,及其在血管内皮氧化应激损伤中的作用,通过western bloting和细胞钙荧光测定,观察阿托伐他汀预处理对小鼠主动脉内皮细胞TRPM2蛋白表达水平和通道开放的影响,并采用离体主动脉环灌流技术,观察阿托伐他汀对H;O;诱导血管内皮功能损伤的改善作用.研究结果表明:经阿托伐他汀预处理7天,可降低小鼠主动脉内皮细胞TRPM2蛋白的表达水平,抑制H;O;引起的TRPM2通道开放介导的细胞内钙升高,减轻H;O;引起的内皮细胞死亡;经阿托伐他汀急性预处理30 min,可抑制H;O;引起的细胞内钙升高;经阿托伐他汀灌胃14天,可减轻H;O;引起的小鼠主动脉环内皮依赖性舒张功能损伤;在TRPM2基因敲除小鼠内,阿托伐他汀对血管舒张功能无明显保护作用.由此可见,阿托伐他汀可通过抑制TRPM2通道的表达和开放来减轻血管内皮氧化应激损伤.

To investigate the effect of atorvastatin on the expression and function of transient receptor potential channel M2(TRPM2),and the role of atorvastatin in oxidative stress injury of vascular endothelium.Western blotting and cell calcium fluorescence assay were used to observe the effect of atorvastatin pretreatment on TRPM2 protein expression and channel opening in mouse aortic endothelial cells.In addition,the isolated aortic ring perfusion was used to observe the improvement effect of atorvastatin on H;O;-induced vascular endothelial dysfunction.The results showed that atorvastatin pretreatment for 7 days decreased the expression of TRPM2 protein in mouse aortic endothelial cells,inhibited the increase of intracellular calcium mediated by H;O;-induced TRPM2 channel opening and alleviated the H;O;-induced death of endothelial cells.Acute pretreatment with atorvastatin for 30 min also inhibited the H;O;-induced increase of intracellular calcium.Atorvastatin attenuated the H;O;-induced injury of endothelium-dependent diastolic function of aortic ring in mice after intragastric administration for 14 days.In TRPM2 knockout mice,atorvastatin had no obvious protective effect on vasodilation.In conclusion,atorvastatin can reduce oxidative stress injury of vascular endothelium by inhibiting the expression and opening of TRPM2 channel.