摘要
目的:观察氯沙坦对兔血管内膜损伤后过氧化物酶体增殖物激活受体-γ(PPARγ)及纤溶酶原激活物抑制因子-1(PAI-1)表达的影响,探讨氯沙坦预防动脉粥样硬化的可能机制和作用。方法:雄性新西兰大白兔24只,随机分为3组:普通饲料喂养组(G1组)、高脂饮食喂饲+动脉内皮损伤组(G2组)及高脂饮食喂饲+动脉内皮损伤+氯沙坦治疗组(G3组)。G2、G3组持续给予胆固醇喂养2周后行腹主动脉内膜剥脱术,G3组内膜剥脱术后第1天开始口服氯沙坦10 mg/kg。3组均于6周后取兔腹主动脉行病理形态学观察和免疫组织化学分析PPARγ和PAI-1蛋白表达,RT-PCR方法检测PPARγ和PAI-1 mRNA的表达。结果:高胆固醇喂养6周后,3组之间内膜厚度(IT)、内膜厚度与中膜厚度比(IT/MT)、内膜面积(IA)、内膜面积与中膜面积比(IA/MA)比较,差异均有统计学意义(F分别为48.700、69.100、133.200和97.500,P均<0.001)。3组之间PPARγ和PAI-1蛋白阳性表达率比较,差异均有统计学意义(F分别为13.800、26.500、9.200和17.400,P均<0.05)。结论:氯沙坦可抑制血管损伤后的内膜增生并改善血管重构,其机制可能与调节PPARγ,从而影响PAI-1水平,改善动脉粥样硬化有关。
Aim ： To observe the effects of angiotensin type 1 receptor antagonist losartan on the expression of peroxi- some proliferators-activated reeeptor-γ （PPARγ） and plasminogen activator inhibitor-1 （PAI-1） after balloon injury in rab- bits,and to explore the possible mechanism of losartan in preventing atherosclerosis. Methods： A total of twenty-four male rabbits were randomly divided into three groups ： ordinary feeding rabbits （ G1 ） ,cholesterol feeding ＋ abdominal artery inju- ry rabbits （ G2）, and cholesterol feeding ＋ abdominal artery injury ＋ losartan treatment rabbits （ G3 ）. The latter two groups were constantly fed with cholesterol diet for 6 weeks and underwent intimal denudation in the abdominal artery after a two- week cholesterol diet. G3 group was orally given losartan （ 10 mg/kg） 1 day after intimal denudation in the abdominal ar- tery. Then the arteries were prepared for histological observation. The expressions of PPAR~ and PAI-1 protein and mRNA were measured by immunohistoehemistry method and RT-PCR. Results： At the end of 6 weeks, the intimal thickness （IT）, IT/media thickness（MT） ratio, intimal area （IA）, IA/media area（MA） ratio among 3 groups were different（ F was 48. 700,69. 100,133. 200, and 97. 500, P 〈 0. 001 ）. The protein and mRNA expressions of PPARγ and PAI-1 among 3 groups were different（ F was 13. 800,26. 500,9. 200, and 17. 400, P 〈 0.05 ）. Oonclusion ： Losartan could inhibit intireal proliferation and improve vessel remodeling after balloon injury. The mechanism of anti-atherosclerosis by losartan may be related to elevation of PPARγand the expression of PAI-1.
出处
《郑州大学学报（医学版）》
CAS
北大核心
2010年第2期293-296,共4页
Journal of Zhengzhou University(Medical Sciences)
