不同剂量瑞舒伐他汀对实验性动脉粥样硬化大鼠过氧化及血管平滑肌增生的影响  

Influence of different doses rosuvastatin on peroxidation and proliferation of vascular smooth muscle cells for experimental atheriosclerosis rats

作　　者：刘爱宁 杨文刚 鞠树红 聂丹凤 周晖[2] 

机构地区：[1]上海市普陀区利群医院神经内科,上海200333 [2]第二军医大学附属长征医院神经内科,上海200003

出　　处：《河北医科大学学报》2015年第2期133-136,共4页Journal of Hebei Medical University

基　　金：上海市普陀区卫生系统自主创新科技资助项目(KW-2012-02)

摘　　要：目的观察不同剂量瑞舒伐他汀对动脉粥样硬化大鼠过氧化及血管平滑肌增生的影响。方法将46只大鼠随机分为5组。对照组(n=6)给予普通饲料喂养;高蛋氨酸组(n=10)在此基础上加质量分数2%的蛋氨酸;叶酸组(n=10)在高蛋氨酸饲料喂养4周后,叶酸按每天0.8 mg/kg剂量灌胃;瑞舒伐他汀低剂量组(n=10)和高剂量组(n=10)以高蛋氨酸饲料喂养4周后,瑞舒伐他汀分别按每天1、2 mg/kg剂量灌胃。末次灌胃后4 h处死动物取血及颈主动脉。检测各组大鼠血浆同型半胱氨酸(homocysteine,Hcy)、血浆丙二醛(malondialdehyde,MDA)含量、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)活性及炎症因子表达,测量颈动脉内膜中膜厚度。结果建模后12周,各组血浆Hcy水平均较建模前显著升高,依次为高蛋氨酸组>叶酸组>低剂量组>高剂量组>对照组(P<0.05);瑞舒伐他汀组各过氧化、炎症指标均显著优于高蛋氨酸组,高剂量组MDA、肿瘤坏死因子α、白细胞介素8及基质金属蛋白酶9含量较低剂量组降低,GSH-PX活性则明显增强(P<0.05);高蛋氨酸组、叶酸组与低剂量组颈动脉内膜中膜厚度明显高于对照组、高剂量组(P<0.05)。结论高剂量瑞舒伐他汀对高Hcy性动脉粥样硬化的疗效更佳,可达到更好的过氧化抑制作用,降低动脉血管平滑肌厚度。Objective To explore the influence of different doses rosuvastatin on peroxidation and proliferation of vascular smooth muscle cells for experimental atheriosclerosis rats.Methods Forty-six male rats were divided randomly into five groups,control group（n = 6）was given with ordinary feed,high methionine group（n=10） with 2%methionine on this basis,folic acid group（n = 10） with high methionine feed after four weeks,adding folic acid for lavage by0.8 mg/kg per day,low dose group（w = 10） and high dose group（n = 10） with high methionine feed after four weeks,adding rosuvastatin for lavage by 1 mg/kg per day,2 mg/kg per day,respectively.The rats were executed after last lavage for four hours to get blood and carotid artery.Plasma homocysteine（Hcy）,content of plasma malondialdehyde（MDA）,activity of glutathione peroxidase（GSH-PX） and inflammatory factors were detected,and the relative thickness of carotid artery walls was measured.Results At 12 weeks after modeling,the level of plasma Hcy was significantly increased than before modeling,the order was high methionine group〈 folic acid〈 low dose group〈 high dose group〈control group（P〈0.05）.The peroxide and inflammatory indexes in rosuvastatin group were significantly better than those of high methionine group.Compared with low dose group,content of MDA,tumor necrosis factor-α,interleukin 8 and matrix metalloproteinases 9 decreased,the activity of GSH-PX was significantly enhanced in high dose group（P〈0.05）.The relative thickness of carotid artery walls in high methionine,folic acid group and low dose group was obviously higher than that of control group,high dose group（P 0.05）.Conclusion High dose of rosuvastatin has better effect of atherosclerosis caused by hyperhomocysteinemia,and can achieve better inhibitory effect on peroxide,decrease the thickness of artery vascular smooth muscle more remarkably.

关 键 词：动脉硬化 瑞舒伐他汀 肌 平滑 

分 类 号：R543.5[医药卫生—心血管疾病]