自发性高血压大鼠肥厚左心室的蛋白质组学研究  

Proteomic Analysis of Hypertrophied Left Ventricle in Spontaneously Hypertensive Rats

作　　者：金贤[1] 夏立[2] 王立顺[2] 石均芝[1] 方宁远[1] 

机构地区：[1]上海交通大学医学院附属仁济医院老年病科,上海200001 [2]上海交通大学医学院病理生理教研室,上海200025

出　　处：《中华高血压杂志》2008年第3期230-234,共5页Chinese Journal of Hypertension

基　　金：国家自然科学基金资助项目(30670830)

摘　　要：目的心肌肥厚是高血压患者心血管事件发生和死亡的主要危险因素,其机制仍未完全阐明。应用双向凝胶电泳/质谱的经典蛋白质组学方法,比较不同年龄自发性高血压大鼠(SHR)肥厚心肌的蛋白质表达谱的差异。方法取4周、20周龄雄性 SHR 和 WKY 大鼠,观察血压和心肌肥厚情况;抽提其左心室组织蛋白,经二维凝胶电泳(2-DE)分离蛋白,银染后计算机图象分析寻找蛋白表达差异点,并以基质辅助激光解吸电离-飞行时间-飞行时间质谱测量法(MALDI-TOF-TOF MS)分析鉴定蛋白。结果 SHR 在血压末升高时就已存在心肌肥厚。经二维胶图比较共找出27个差异蛋白点,质谱分析鉴定出20个差异蛋白,涉及能量代谢、线粒体氧化磷酸化和氧化应激反应等。其中13个蛋白的变化发生在4周龄 SHR 血压未升高时;另7个蛋白表达变化发生于20周龄血压持续升高状态下的 SHR 肥厚心肌中。结论 SHR 肥厚心肌中脂肪酸氧化和葡萄糖有氧氧化中的酶下调,而糖酵解的关键酶明显上调,且这些变化大多发生在血压升高前;线粒体氧化磷酸化的多种酶和一些参与抗氧化作用的蛋白均发生了变化,提示在 SHR 的心肌肥厚过程中物质能量代谢和氧化应激也具有重要作用。Objective To investigate the molecular mechanisms for the development of cardiac hypertrophy in hypertension, the present study provided the differential protein expression analysis of hypertrophied heart at different stages in spontaneously hypertensive rats （SHR）. Methods The profiles of protein expression of left ventricular myocardium in SHR and its normotensive control Wistar-Kyoto （WKY） rats at the age of 4 and 20 weeks were analyzed with two-dimensional gel electrophoresis （2-DE） in combination with matrix assisted laser desorption ionization-time of flight （MALDI-TOF-TOF） mass spectrometry. Results Although the blood pressure of SHR was normal at 4 weeks age, hypertrophy of the left ventricle had already developed. The expression pattern in the hypertrophic myocardium was found 27 modulated proteins, 20 of which were identified. These proteins are involved in reactions of energy metabolism, mitochondrial oxidative phosphorylation and oxidative stress, etc. The expression of 13 proteins was significantly changed in SHR rats at early stage prior to the development of sustained hypertension, while the expression changes of other 7 proteins occurred only at [ate stage in SHR rats when the blood pressure was significantly elevated. Conclusions Increase in glycolysis and decrease in oxidation of fatty acid and glucose was shown in the hypertrophied myocardium from early stage in SHR prior to the development of hypertension. The significant changes in protein expression of the mitochondrial electron transport chain and antioxidative molecules support the hypothesis that oxidative stress promotes and accelerates the development of hypertensive cardiac hypertrophy.

关 键 词：心肌肥厚 高血压 蛋白质组学 自发性高血压大鼠 

分 类 号：R541.3[医药卫生—心血管疾病]