瑞舒伐他汀对动脉内膜损伤糖尿病大鼠动脉粥样硬化及屏氧酶-1的影响  

Effects of rosuvastatin on atherosclerosis and paranoxonase-1 of diabetic model rats with coronary artery trauma

作　　者：张曼[1] 佟浩[2] 孙晓[1] 

机构地区：[1]沈阳医学院奉天医院循环内科,辽宁沈阳110024 [2]中国医科大学解剖学教研室,辽宁沈阳110001

出　　处：《中国新药与临床杂志》2010年第10期762-765,共4页Chinese Journal of New Drugs and Clinical Remedies

基　　金：沈阳市科学计划项目(1071165-9-00;1091138-9-00);辽宁省自然科学基金(20092073)

摘　　要：目的研究瑞舒伐他汀对动脉内膜损伤的糖尿病大鼠血脂、动脉粥样硬化和屏氧酶-1(PON1)的作用及其机制。方法 Wistar大鼠48只,随机分为正常对照组、模型组和瑞舒伐他汀组,均n=16。正常对照组给予普通饮食32 wk后生理盐水灌胃2 mo,模型组与瑞舒伐他汀组高脂饮食20 wk后采用链脲佐菌素诱导糖尿病辅助球囊损伤主动脉内膜制模,继续高脂饮食12 wk后分别给予生理盐水和瑞舒伐他汀20 mg.kg-1灌胃2 mo。观察血脂和主动脉内膜形态学改变,并检测PON1的含量、mRNA表达及活性改变。结果与正常对照组相比,模型组大鼠主动脉内膜增生明显,总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平明显增高(P<0.01),高密度脂蛋白胆固醇(HDL-C)水平明显降低(P<0.01),PON1表达减少,活性显著下降(P<0.01);与模型组相比,瑞舒伐他汀组TC、TG、LDL-C均显著降低(P<0.05或P<0.01),HDL-C水平呈上升趋势(P>0.05),主动脉内膜增生改善,PON1活性增高、mRNA表达增加(P<0.05或P<0.01)。结论瑞舒伐他汀可降低血脂,通过增加PON1的表达及活性提高HDL-C抗氧化能力,达到延缓动脉粥样硬化的作用。AIM To observe the effects and mechanisms of rosuvastatin on lipid,atherosclerosis and paranoxonase-1（PON1） in diabetic model rats with coronary artery trauma.METHODS Forty-eight Wistar rats were randomly divided into control group,model group and rosuvastatin group,n = 16 respectively.The rats in the control group were given saline for 2 month after fed with normal diet for 32 weeks.The rats in the model group and the rosuvastatin group were induced diabetes by streptozotocin assisted with balloon induced aortic intima injury after fed with high cholesterol diet for 20 weeks,and continued with high cholesterol diet for 12 weeks.Then saline or rosuvastatin 20 mg.kg-1 were given orally for 2 month,respectively.Lipid,HE staining of aorta,PON1 concentration,PON1 mRNA expression and PON1 activity were measured.RESULTS HE staining showed that atherosclerotic changes and luminal surface of the aorta in the model group increased.The levels of total cholesterol（TC）,triglyceride（TG）,low density lipoprotein cholesterol（LDL-C） increased,high density lipoprotein cholesterol（HDL-C）,PON1 mRNA expression and PON1 activity decreased in the model group as compared with the control group（P 0.01）.In the rosuvastatin group,the level of TC,TG,LDL-C decreased,PON1 concentration,PON1 mRNA expression and PON1 activity increased as compared with the model group（P 0.05 or P 0.01）.CONCLUSION Rosuvastatin could decrease lipid and inhibit the atherosclerosis by improved the function and activity of PON1.

关 键 词：瑞舒伐他汀 动脉硬化 脂蛋白类 HDL 屏氧酶-1 

分 类 号：R972.6[医药卫生—药品]