CAJ | 학술논문

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、5 mg/kg和20 mg/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5 mg/kg和20 mg/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20 mg/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20 mg/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.
목적 관찰서서벌타정대혈관내피점부성급양화응격적억제작용.방법 재지단백E(apoE)기인고제서80지,C57BL/6소서20지,균위8～9주령.장apoE기인고제서분위2、6주모형대조조각10지화약물치료조각30지,C57BL/6소서분위2、6주정상대조조각10지.치료조매일1차피하주사불동농도적서서벌타정,제량분별위1、5 mg/kg화20 mg/kg;약물처리만2주혹6주시,심내천자취혈,병수획소서주동맥.결과 치료조경서서벌타정5 mg/kg화20 mg/kg치료후,혈장총담고순명현하강,2주시위(480.7±35.3)mmol/L화(371.5±27.1)mmol/L,6주시위(400.1±37.6)mmol/L화(305.0±19.3)mmol/L,여상응모형대조조[2주(675.0±42.0)mmol/L화6주(660.0±44.3)mmol/L]비교,차이유통계학의의(P＜0.05혹P＜0.01);단삼선감유화고밀도지단백담고순균무명현변화.치료조경서서벌타정20 mg/kg치료2주후,주동맥내피단핵세포점부솔교모형대조조명현하강,분별위(2.24±0.72)%화(3.76±2.53)%(P＜0.05);6주후하강경위명현,분별위(1.94±0.40)%화(3.95±2.61)%(P＜0.01).서서벌타정환가억제소서주동맥세포색소b245(P22phox)표체화활성양물질산생,량자표체모형대조조분별위(3.22±1.53)%화(4.75±2.62)μg/L,서서벌타정20 mg/kg치료6주후,분별위(1.41±0.72)%화(2.72±0.88)μg/L,차이균유통계학의의(P＜0.05).결론 서서벌타정구유억제혈관내피점부성급항양화응격적작용.
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)knockedout 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;6weeks:(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 p22phox and superoxide production[0 mg/kg for 6 weeks group:(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.