氯沙坦和卡托普利对高脂饮食兔动脉粥样硬化形成和纤溶功能的影响

目的 :探讨氯沙坦和卡托普利对高脂饮食家兔动脉粥样硬化形成和纤溶功能的影响及机制。方法 :健康雄性家兔 4 0只随机分为 4组 :A组予普通饲料、B组予 1%高胆固醇饲料、C组和D组进食同B组 ,分别予氯沙坦和卡托普利灌胃。 12wk后取血检测各项生化指标 ,处死动物 ,制作标本 ,观察主动脉粥样斑块形成情况和血管内膜、中膜的组织形态学改变及内膜的超微结构 ;检测血管组织的内皮素 (ET 1)水平。结果 :B组的血脂和ET 1水平较A组明显增高 ,斑块形成明显 ,血浆t PA活性降低、PAI 1活性增高。氯沙坦的干预不影响血脂水平 ,但可减小斑块面积 ,降低ET 1,改善t PA和PAI 1活性 ;D组除ET 1外的各项指标与C组无统计学差异。C组和D组内皮损伤明显轻于B组。结论 :氯沙坦和卡托普利均能改善高脂血症家兔的内皮纤溶功能 ,减轻粥样斑块形成。

Effects of losartan and captopril on fibrinolytic function and formation of atherosclerosis in cholesterol-fed rabbits

AIM:To investigate mechanism and effects of losartan and captopril on the fibrinolytic function and formation of experimental atherosclerosis in cholesterol fed rabbits. METHODS: Forty healthy male rabbits were randomly divided into four groups. Group A received normal chow, group B,C,D were submitted to 1 % cholesterol and 5 % lard enriched diet ,at the same time, group C was irrigated stomaches with losartan 25 mg·kg -1 ·d -1 and group D with captopril 12.5 mg·kg -1 ·d -1 . After 12 wk, blood samples were obtained for detection of serum lipids levels, plasma tissue type plasminogen activator (t PA) and plasminogen activator inhibitor (PAI 1) activities. Then all animals were killed and chests were opened to get the aortas. General specimens were made to estimate the atherosclerotic lesion. Ordinary pathological and electron microscope's sections were made to observe the histopathological changes of blood vessels, ultrastructure of intima. Rest aortic segments were made into homogenate for examination of the endothelin 1(ET 1) levels. RESULTS: Serum lipids and endothelin 1 levels of group B were significantly higher( P <0.01) than those of group A. The aortic atherosclerotic lesions were more severe than those of group A, and plasma t PA activity was lower ( P <0.05) in atherosclerosis and PAI 1 activity was higher than that of Group A ( P <0.05). Through treatment with losartan or captopril, the serum lipids levels were not altered, but all area of atherosclerotic lesions, injury of endothelium, intima thickening reduced, and t PA activity and PAI 1 activity improved ( P <0.05) in group C or D. The differences between group C and group D were not significant ( P >0.05). Additionally, ET 1 levels decreased significantly after treatment with losartan( P <0.01) while those treated with captorpil did not. The injury of endothelium of group C and D was significantly milder than that of Group B. CONCLUSION:Both losartan and captopril have the beneficial effects of ameliorating the fibrinolytic function and reducing atherosclerotic lesion of cholesterol fed rabbits.