西罗莫司联用阿托伐他汀对大鼠血管平滑肌细胞氧化应激损伤和一氧化氮合酶的影响

目的探讨西罗莫司和阿托伐他汀联合使用对大鼠血管平滑肌细胞氧化应激损伤和一氧化氮合酶(NOS)的影响。方法取大鼠血管平滑肌细胞进行实验,分为空白组、DMSO组、西罗莫司组(100nmol/L)、阿托伐他汀组(3μmol/L)和联合组(西罗莫司100nmol/L加阿托伐他汀3μmol/L)。实验各组细胞给予相应药物干预2h后,加入三丁基过氧化氢诱导氧化应激损伤,24h后检测各项指标。结果与空白组比较,DMSO组、西罗莫司组、阿托伐他汀组和联合组细胞增殖率明显下降(P<0.01)。与空白组和DMSO组比较,阿托伐他汀组和联合组超氧化物歧化酶水平明显上升和丙二醛水平明显下降(P<0.05,P<0.01)。与空白组、DMSO组、西罗莫司组比较,阿托伐他汀组和联合组诱导型一氧化氮合酶(iNOS)mRNA和蛋白表达明显下降(P<0.01);联合组iNOS mRNA和蛋白表达较阿托伐他汀组明显下降(P<0.05,P<0.01)。结论在氧化应激状态下,西罗莫司和阿托伐他汀均能抑制大鼠血管平滑肌细胞增殖和抗氧化损伤,维持NOS系统平衡,联合应用的效果优于单独应用。

Effect of combined sirolimus and atorvastatin on oxidative stress injury and nitric oxide synthases in rat vascular smooth muscle cells

Objective To study the effect of combined sirolimus and atorvastatin on oxidative stress injury and nitric oxide synthase(NOS)in rat vascular smooth muscle cells(VSMC).MethodsRat VSMC were divided into control group,dimethyl sulfoxide(DMSO)group,sirolimus(100 nmol/L)group,atorvastatin(3μmol/L)group,combined sirolimus(100nmol/L)and atorvastatin(3μmol/L)group.Two hours after the 4experimental groups were treated with corresponding drugs,oxidative stress was induced with tert-butyl hydroperoxide.Different indexes were detected after 24h,including cell proliferation,superoxide dismutase(SOD),malonyldialdehyde(MDA), eNOS,iNOS mRNA and protein expressions.Results The cell proliferation rate was significantly lower in 4experimental groups than in control group(P<0.01).The SOD level was significantly higher while the MDA level was significantly lower in atorvastatin group and combined sirolimus and atorvastatin group than in control group and DMSO group(P<0.05,P<0.01).The expression levels of iNOS mRNA and protein were significantly lower in atorvastatin group and combined sirolimus and atorvastatin group than in control group,DMSO group and sirolimus group(P<0.01)and in combined sirolimus and atorvastatin group than in atorvastatin group(P<0.05, P<0.01).Conclusion Combined sirolimus and atorvastain inhibits proliferation of rat VSMC,attenuates oxidative stress,and maintains NOS system balance.The effect of combined sirolimus and atorvastain is better than that of atorvastatin or sirolimus.