瑞舒伐他汀对载脂蛋白E基因敲除小鼠血管内皮黏附性和氧化应激的抑制作用

Rosuvastatin attenuates vascular endothelial adhesiveness and oxidative stress in apoE knocked-out mice

目的观察瑞舒伐他汀对血管内皮黏附性及氧化应激的抑制作用。方法载脂蛋白E（apoE）基因敲除鼠80只。C57BL／6小鼠20只，均为8～9周龄。将apoE基因敲除鼠分为2、6周模型对照组各10只和药物治疗组各30只，C57BL／6小鼠分为2、6周正常对照组各10只。治疗组每日1次皮下注射不同浓度的瑞舒伐他汀，剂量分别为1、5mg／kg和20mg／kg；药物处理满2周或6周时，心内穿刺取血，并收获小鼠主动脉。结果治疗组经瑞舒伐他汀5mg／kg和20mg／kg治疗后，血浆总胆固醇明显下降，2周时为（480．7±35．3）mmol／L和（371．5±27．1）mmol／L，6周时为（400．1±37．6）mmol／L和（305．0±19．3）mmol／L，与相应模型对照组[2周（675．0±42．0）mmol／L和6周（660．0±44．3）mmol／L]比较，差异有统计学意义（P〈0．05或P〈0．01）；但三酰甘油和高密度脂蛋白胆固醇均无明显变化。治疗组经瑞舒伐他汀20mg／kg治疗2周后，主动脉内皮单核细胞黏附率较模型对照组明显下降，分别为（2．24±0．72）％和（3．76±2．53）％（P〈0．05）；6周后下降更为明显，分别为（1．94±0．40）％和（3．95±2．61）％（P〈0．01）。瑞舒伐他汀还可抑制小鼠主动脉细胞色素b245（P22phox）表达和活性氧物质产生，两者表达模型对照组分别为（3．22±1．53）％和（4．75±2．62）μg／L，瑞舒伐他汀20mg／kg治疗6周后，分别为（1．41±0．72）％和（2．72±0．88）μg／L，差异均有统计学意义（P〈0．05）。结论瑞舒伐他汀具有抑制血管内皮黏附性及抗氧化应激的作用。

Objective To investigate whether rosuvastatin has the effects of anti-oxidative stress and attenuates vascular endothelial adhesiveness on the vessel wall in apolipoprotein E（apoE） knocked- out mice. Methods Eighty 8-week-old apolipoprotein E-deficient mice and twenty 8-week-old C57BL/6 mice, were fed a normal chow diet for 12 weeks, and were divided into 2 weeks treatment group and 6 weeks treatment group, apoE knocked-out mice were subcutaneously injected with rosuvastatin at a dose of 1, 5, or 20 mg/kg daily for 2 or 6 weeks prior to sacrifice. Blood sample was taken by cardiopuncture and the aorta was obtained at the end of the 2th or 6th weeks. Results Total cholesterol level was significantly decreased after 2 or 6 weeks of 5, or 20 mg/kg rosuvastatin treatment（2 weeks： （480.7±35.3）mmol/L, （371.5 ± 27. 1 ）mmol/L; 6 weeks： （400.1 ± 37.6） mmol/ L, （305.0± 19.3） mmol/L], compared with 0 mg/kg group （20 weeks： （ 675.0 ± 42.0 ） mmol/L; 6 weeks： （660.0±44.3）mmol/L] （P〈0.05 or 0.01）. But the changes of triglyceride and high-density lipoprotein were not like the above. The endothelial adhesiveness for monocytes was significantly attenuated after 2 weeks in 20 mg/kg group versus 0 mg/kg group （（2.24± 0.72）% vs. （3.76 ± 2.53） %]（P〈0.05）, and even more significantly after 6 weeks in 5, 20 mg/kg groups[（1.94± 0.40） %, （3.95 ± 2.61 ） %] （ P 〈 0.01 ）. In addition, rosuvastatin inhibited vascular expression of p22phoxandsuperoxideproduction（0 mg/kg for 6 weeksgroup：（3.22±1.53）%, （4.75±2.62）μg/ L; 20 mg/kg for 6 weeks group： （1.41±0.72）% , （2.72±0.88）μg/L] （all P〈0.05） . Conclusions Rosuvastatin has a role of anti-oxidative stress and attenuates vascular endothelial adhesiveness on the vessel wall.