雷帕霉素联用阿托伐他汀减轻大鼠血管平滑肌细胞氧化应激损伤  

Rapamycin combined with atorvastatin attenuate oxidative stress injury in rat vascular smooth muscle cells

作　　者：傅国华[1] 龚勋[1] 吴赛珠[1] 詹琼[1] 董海德[2] 赖文岩[1] 

机构地区：[1]南方医科大学南方医院心内科,广东广州510515 [2]从化市人民医院ICU,广东从化510900

出　　处：《热带医学杂志》2013年第5期538-541,576,共5页Journal of Tropical Medicine

基　　金：国家"973"项目子课题(2007CB507404)

摘　　要：目的探讨雷帕霉素与阿托伐他汀联用对大鼠血管平滑肌细胞氧化应激损伤的影响。方法取大鼠血管平滑肌细胞进行实验,随机分为空白对照组、DMSO组、阿托伐他汀(3μmol/L)组(A3组)、雷帕霉素50nmol/L组(R50组)、雷帕霉素100nmol/L组(R100组)、联用组(阿托伐他汀加雷帕霉素100nmol/L)。实验各组细胞给予相应药物干预2h后,加入三丁过氧化氢(t-BHP)刺激诱导氧化应激损伤,24h后检测各项指标。结果与空白对照组相比,DMSO组细胞SOD活力、MDA含量及β-Gal染色率差异无统计学意义,而其细胞增殖率降低(P<0.01)。各药物干预组细胞SOD活力、MDA含量、β-Gal染色率和细胞增殖率与空白对照组和DMSO组比较差异均有统计学意义(P均<0.05);而A3组和R50组比较上述指标差异无统计学意义,R100组与A3组和R50组比较上述指标差异有统计学意义(P均<0.05);联用组细胞SOD活力较其余各组明显升高(P<0.01),而MDA含量、β-Gal染色率和细胞增殖率较其余各组则均明显降低(P均<0.05)。而内皮型一氧化氮合酶(eNOS)在大鼠血管平滑肌细胞中无表达。结论在氧化应激状态下,阿托伐他汀及雷帕霉素均具有抑制大鼠血管平滑肌细胞增殖、抗氧化损伤的作用,从而维护血管平滑肌细胞的正常功能并能延缓其衰老,两药联用的效果优于两药单独应用。Objective To explore the effect of the combination of rapamycin and atorvastatin on oxidative stress injury in the rat vascular smooth muscle cells. Methods Rat vascular smooth muscle cells were isolated from rat aorta and cultured. They were divided into six groups： control, DMSO, atorvastatin 3 μmo｜/L（A3）, rapamycin 50 nmol/L（R50）, rapamycin 100 nmol/L（R100） and atorvastatin combined with rapamycin 100 nmol/L. After pretreated with corresponding stimulants for 2 hours,VSMCs were treated with t-BHP to induce oxidative stress.After 24 hours of incubation, superoxide dismutase （ SOD ）, malonyldialdehyde （ MDA ）, senescence associated - β-galactose （ SA - β- GAL ）, cell proliferation （CCK8）, mRNA and protein expression of eNOS were determined. Results Compared with control group, the leveles of SOD, MDA and SA-β-GAL of the DMSO group did not change, but the cell proliferation rate was decreased. In other four groups,MDA and SA-β-GAL senescence rates were decreased,while the SOD level was increased. There was no significant statistical difference between A3 group and R50 group. Compared with R50 or A3 groups, SOD level was higher in R100 group and the MDA,SA-β-GAL rates and cell proliferation rates were decreased. In the combination group, the SOD level was higher than that of any other groups,while the MDA,SA-β-GAL rates and cell proliferation rates were lower. Conclusion Rapamycin combined with atorvastain can inhibit proliferation of rat VSMCs, attenuate oxidative stress, and delay senescence more greately than either atorvastatin or rapamycin monotherapy.

关 键 词：雷帕霉素 阿托伐他汀 大鼠血管平滑肌细胞 氧化应激 衰老 

分 类 号：R543.5[医药卫生—心血管疾病]