摘要目的 酒精性心肌病形成过程中发生肾素-血管紧张素系统(RAS)激活、能量代谢紊乱和心脏重构,本研究探讨RAS和过氧化物酶体增殖物激活受体(PPAR)α和PPARγ在酒精性心肌病发病机制中的作用.方法 实验动物分为3组,即酒精组、酒精+厄贝沙坦组、对照组.采用逆转录聚合酶链反应和免疫印迹方法检测心肌RAS系统相关指标mRNA、PPARα和PPARγ蛋白表达,放射免疫法测定RAS系统活性,光镜、电镜和超声法检测心脏结构和功能.结果 (1)与对照组比较,酒精组心肌血管紧张素(Ang)Ⅰ、Ang Ⅱ和肾素浓度在酒精性心肌病形成过程中(0到6个月)渐次升高(P<0.05).(2)6个月时,酒精组心肌组织肾素、血管紧张素原、血管紧张素转化酶和血管紧张素Ⅱ1型受体表达高于对照组(P<0.05).(3)2、4和6个月时,酒精组和酒精+厄贝沙坦组心肌组织PPARα蛋白表达渐次减少(酒精组PPARα蛋白表达量分别为50.30%、34.3%和27.1%,酒精+厄贝沙坦组分别为86.4%、75.4%和59.4%),均少于对照组(P分别<0.01,0.05),且酒精组蛋白表达量低于酒精+厄贝沙坦组(P<0.05).(4)6个月时,酒精组、酒精+厄贝沙坦组PPARγ蛋白表达低于对照组(P分别<0.01,0.05),且酒精组表达量低于酒精+厄贝沙坦组(P<0.05).结论 RAS系统激活、PPARα和PPARγ蛋白表达异常与酒精性心肌病进展相关,RAS表达和PPARα及PPARγ蛋白改变可能存在紧密联系.

abstractsObjective To explore the time course of renin-angiotensin system (RAS), peroxisome proliferator-activated receptor (PPAR)α and PPARγ change in an animal model of alcoholic cardiomyopathy (ACM).Methods Adult rats were divided into three groups: ACM group (A, 10% alcohol as drinking water plus 5 ml 60% alcohol · kg-1 · d-1 per gavage in the 1st week;10% alcohol as drinking water plus 10 ml 60% alcohol/kg bid per gavage in the 2nd week,20% alcohol as drinking water plus 15 ml 60% alcohol/kg bid per gavage during week 3 to week 16), ACM/ARB group(B, A + Irbesartan 5 mg·kg-1 · d-1 per gavage ) and control group (C).mRNA expressions and activities of renin, angiotensin, ACE and AT1 were detected with RT-PCR and radioimmunoassay methods.Protein expressions of PPARα and PPARγ were determined with Western blot.Echocardiogram, optic (HE) and electron microscope examinations were also performed.Parameters were obtained at 2 or 6 months (n =7-10 each).Results Compared with group C, LV/BW ratio was significantly increased and LVEF significantly decreased, activities and expressions of Ang Ⅰ , Ang Ⅰ and renin were gradually increased, protein expressions of PPARα were gradually decreased at 2 and 6 months in group A (all P < 0.05) .These changes could be partly attenuated by Irbesartan.conclusion Activated RAS and decreased protein expressions of PPARα and PPARγ contributed to the development of ACM.