酒精性心肌病大鼠过氧化酶体增殖物激活受体α和类维甲酸受体α的表达以及肉毒碱干预  

Peroxisome proliferator-activated receptor α and retinoid X receptor α expressions and intervention in alcohofic cardiomyopathy rats

作　　者：井玲[1] 李为民[1] 周立君[1] 杨宝峰[2] 

机构地区：[1]哈尔滨医科大学附属第一医院心内科,150001 [2]哈尔滨医科大学

出　　处：《中华心血管病杂志》2009年第4期324-329,共6页Chinese Journal of Cardiology

基　　金：黑龙江省青年科学技术专项资金资助项目（QC07C89）;黑龙江省教育厅科学技术研究指导资助项目（11533040）;哈尔滨医科大学附属第一医院科研基金资助项目（2007119）

摘　　要：目的探讨过氧化酶体增殖物激活受体（PPAR）α和类维甲酸受体（RXR）α在酒精性心肌病（ACM）中的表达以及肉毒碱干预疗效和可能机制。方法雄性Wistar大鼠90只分为3组：酒精组、酒精＋药物组和对照组。每组30只。6个月后使用免疫组化法检测心肌组织Ⅰ型胶原、Ⅲ型胶原、基质金属蛋白酶-9（MMP-9）和信号转导蛋白-3（Smad-3）的蛋白表达，Western blot法测定心肌组织PPARα和RXRα蛋白表达。结果酒精组和酒精＋药物组Ⅰ型胶原、Ⅲ型胶原、MMP-9和Smad-3蛋白表达显著高于对照组（P〈0．01和0．05），PPARα和RXRα蛋白表达（酒精组分别为0．156和0．192，酒精＋药物组分别为0．248和0．385）显著少于对照组（P〈0．01和0．05）。酒精组与酒精＋药物组比较，Ⅰ型胶原、Ⅲ型胶原、MMP-9、Smad-3、PPARα和RXRα蛋白表达具有显著差异（P〈0．05）。PPARα和RXRα与左心室射血分数和左心室短轴缩短率呈显著正相关（P〈0．01），与左心室舒张末期内径、Ⅰ型胶原、Ⅲ型胶原、MMP-9和Smad-3呈显著负相关（P〈0．01）。结论酒精性心肌病进展中PPARα和RXRα蛋白表达下调，心脏重构和心肌纤维化形成。肉毒碱可能通过PPARα和RXRα代谢途径改善心脏重构和心肌纤维化。Objective To investigate the effects of carnitine on cardiac function, collagen contents, peroxisome proliferator-activated receptor α （PPARα） and retinoid X receptor α （RXRα） expressions in a rat alcoholic cardiomyopathy model. Methods Adult male Wistar rats were randomly divided into alcohol group （A）, alcohol/carnitine group （B） and control group. Six months later, prαein expressions of collagen Ⅰ, collagen Ⅲ, matrix metalloprαeinase-9 （MMP-9） and Smad-3 were determined by immunohistochemical staining. Prαein expressions of PPARα and RXRα were detected by Western blα. Results Expressions of collagen Ⅰ , collagen Ⅲ, MMP-9 and Smad-3 were significantly increased in groups A and B compared to group C （P 〈0. 01 or P 〈0. 05）. Expressions of PPARα and RXRα （0. 156 and 0. 192, respectively, in group A; 0. 248 and 0. 385, respectively, in group B ） were decreased compared to group C （P 〈 0. 01 or P 〈 0. 05 ）. These changes were significantly attenuated by carnitine （all P 〈 0. 05, group B vs. group A）. Moreover, PPARα and RXRα positively correlated with EF and FS, and negatively correlated LVEDd, collagen Ⅰ , collagen Ⅲ, MMP-9 and Smad-3 （ all P 〈 0. 01 ）. Conclusion PPARα and RXRα downregulation is significantly correlated with cardiac dysfunction in this alcoholic cardiomyopathy model, carnitine ameliorated the cardiac fibrosis and remodeling possibly through upregulating the metabolic pathways of PPARα and RXRα.

关 键 词：心肌病 酒精性 PPARΑ 肉碱 类维甲酸受体α 

分 类 号：R686[医药卫生—骨科学]