美托洛尔抑制原发性高血压左室肥大心肌细胞中G蛋白受体激酶2的表达  

Metoprolol Inhibit the Expression of GRK_2 in Hypertrophic Cardiac Myocytes of Spontaneously Hypertensive Rats

作　　者：许德星[1] 林岫芳[2] 易先平[2] 邹燕敦[2] 

机构地区：[1]泉州市第一医院心内科,福建泉州362000 [2]中山大学附属第五医院心内1科,广东珠海519000

出　　处：《中华高血压杂志》2009年第2期167-170,共4页Chinese Journal of Hypertension

基　　金：广东省科技厅项目2007B031510002;珠海市科技局项目PC20071042;珠海市科技计划项目PB20075024资助

摘　　要：背景持续的高血压并发心肌肥大,目前对心肌肥大的机制尚未完全明确,围绕细胞信号转导通路的研究已成为热点;对于心肌肥大的干预治疗,β受体阻滞剂显示出了确切的效果,但其改善心肌重塑的机制尚未明了。目的观察美托洛尔对肥大心肌细胞中G蛋白受体激酶2(GRK2)的影响,探讨美托洛尔改善心肌重塑的可能机制。方法以自发性高血压大鼠(SHR,n=6)为研究对象,通过免疫荧光标记、荧光显微镜及Werstern Blot等方法,检测美托洛尔干预后SHR左心室心肌细胞中GRK2的表达及其分布。WKY大鼠(n=6)为对照组。结果心肌总蛋白中GRK2表达6月龄SHR组和WKY组比较无明显变化(GRK2,6月龄SHR:59.5±1.6比6月龄WKY60.9±2.0,n=6,P>0.05),8月龄SHR比6月龄SHR显著增加(GRK2,8月龄SHR:74.7±1.3比6月龄SHR:59.5±1.6,n=6,P<0.01),均有心肌细胞膜上的聚积,8月龄SHR药物组比非药物组显著减少(GRK2,8月龄SHR药物组:64.7±1.5比8月龄SHR:74.7±1.3,n=6,P<0.01),心肌细胞膜上聚积减少。结论在心肌肥大的过程中,GRK2表达增加并且有心肌细胞膜(闰盘)上的聚积,提示GRK2与心肌肥大有关系,参与心肌肥大细胞信号途径的调控。抑制心肌细胞GRK的表达以及细胞膜上的聚积可能是美托洛尔改善心脏重塑的机制之一。Background and Objective Mechanism governing cardiac hypertrophy complicated by hypertrophy has not entirely clear, however, alteration of cell signaling transduction may be one of the pathway. β adrenergdrenic receptor blockers have been shown reliable effect on cardiac failure, but the mechanism is unclear. The purpose of this study was to study the effect of metoprolol on G protein receptor kinase 2 （GRK2 ） in myocardial hypertrophy and explore its mechanism of improving myocardial remodeling. Methods Using immunofluorescent labeling, fluorescent microscopy and Western Blotting, the expression and subcellular localization of GRK2 in the cardiac myocytes of left ventricle were determined in 8-month-old spontaneously hypertensive rats （ SHR, n = 6 ） fed with metoprolol 25 mg/（kg · d） from 6-month-old, using age and weight matched WKY rats（n=6） as control. Results There were no obvious difference of GRK2 expression between 6-month-old SHR and WKY rats（GRK2, 6M-SHR： 59.5±1.6 to 6M-WKY： 60.9±2.0, n=6, P〉0. 05）, while GRK2 was increased in 8-month-old SHR comparison with 6-month-old SHR（GRK2, 8M-SHR： 74.7±1.3 to 6M-SHR： 59.5±1.6, n=6, P〈0.01）and was attenuated by metoprolol（GRK2, 8M-SHR-D： 64.7±1.5 to 8M-SHR： 74.7±1.3, n=6, P〈0.01）. Metoprolol decreased the membrane translocation of GRK2 increased in 6, 8 month-old SHR rats. Conclusions In the process of cardiac hypertrophy, the manifestation that GRK2 expression and accumulation on cardiac cell membrane （-disk） suggest that GRK2 may play a role in the cell signaling transduction leading to cardiac hypertrophy. One of mechanisms by which metoprolol improved cardiac remodeling may be attributed to inhibit the expression and membrane translocation of GRK2 in the cardiac myocytes.

关 键 词：美托洛尔 G蛋白耦联受体激酶2 高血压 心肌肥大 信号传导 

分 类 号：R541.3[医药卫生—心血管疾病]