卡托普利对高血压左心室肥大心肌细胞中GRK_2表达和亚细胞分布的影响  

Influence of captopril on the expression and redistribution of G protein-coupled receptor kinase 2 in cardiac myocytes of hypertrophic ventricle

作　　者：邹燕敦[1] 林岫芳[1] 许德星[2] 易先平[3] 

机构地区：[1]广东省妇幼保健院,广州510010 [2]中山大学附属第五医院心内科 [3]中山大学附属第五医院病理科

出　　处：《临床心血管病杂志》2009年第5期367-370,共4页Journal of Clinical Cardiology

基　　金：广东省科技厅资助项目(No:2007B031510002);珠海市科技局项目(No:PC20071042)

摘　　要：目的:研究G蛋白偶联受体激酶2(GRK2)在高血压心肌肥大发生发展机制中的作用和卡托普利对心肌中GRK2表达水平、活性及亚细胞分布的影响,探讨卡托普利抑制心肌肥大的机制。方法:通过免疫荧光标记、共聚焦显微镜及Westernblot等方法,检测6月龄的WKY(WKY组)、自发性高血压(SHR,SHRA组)大鼠,8月龄SHR(SHRB组)和卡托普利干预SHR(SHRC组)大鼠左心室心肌细胞中GRK2的表达及其分布。结果:各组大鼠左室心肌组织总蛋白中GRK2表达无明显变化(P>0.05)。细胞质中GRK2表达SHRA组比WKY组表达减少(P<0.01);SHRB组比SHRC组GRK2表达进一步减少(P<0.01);而SHRC组比SHRB组GRK2表达增加(P<0.05)。细胞膜蛋白中GRK2在SHRA组比WKY组表达增加(P<0.01);SHRB组比SHRA组GRK2表达进一步增加(P<0.05);而SHRC组比SHRB组GRK2表达减少(P<0.01)。细胞核蛋白中无GRK2表达。共聚焦显微镜观察发现GRK2在SHR大鼠细胞膜特别是心肌细胞两端的闰盘聚集明显,卡托普利能减少GRK2在细胞膜分布。结论:GRK2与心肌细胞肥大发生发展关系密切,参与心肌肥大细胞信号转导的调控,卡托普利能通过调节GRK2亚细胞分布而发挥抑制心肌肥大作用。Objective：To investigate G protein-coupled receptor kinase 2 （GRK2） in the development of hypertension ventricular hypertrophy mechanism and the role of captopril on GRK2 expression levels, activity and distribution of subcells, to elucidated the suppression mechanism of captopril for cardiac hypertrophy. Method：We examined the effects of captopril on expression and subcellular distribution of GRK2 in the left ventricle of different age spontaneously hypertensive rats （SHR） using immunofluorescent labeling, confocal microscopy and Western blotting. Result：Six-month-old Wistar-Kyoto rats （6M-WKY）, 6-month-old SHR rats （6M-SHR）, 8-month-old SHR rats （8M-SHR） and captopril intervention group SHR rats （8M-SHR-D） GRK2 in the total protein expression of no significant change （P〉0.05）. GRK2 in the cytoplasm of 6M-SHR rats than 6M-WKY rats decreased expression （P〈0.01） 8M-SHR rats than 6M-SHR rats, GRK2 expression further reduced （P〈0.01） and 8M- SHR-D rats than 8M-SHR rats, GRK2 increased expression （P〈0.05）. GRK2 expression in membrane protein of 6M-SHR rats than 6M-WKY rats increased expression （P〈0.01） 8M-SHR rats than 6M-SHR rats, GRKz ex- pression further increase （P〈0.05） and 8M-SHR-D rats than 8M-SHR rats, GRK2 expression reduced （P〈0.01）. No expression of GRK2 in nucleoprotein. We found that GRK2 in SHR rats cardiac cells membrane and at both ends of the intercalated disks gathered particularly evident. Conclusion： Myocardial hypertrophy in the process of development, GRK2 in myocardial hypertrophy of the total protein expression did not change, but in the cytoplasm transferred to the cell membrane, especially in the accumulation of myocardial intercalated disks. No expression of GRK2 in nucleoprotein. Captopril can block GRK2 from the membrane to the cytoplasm transfer. Shows GRK2 close ties with myocardial hypertrophy, involved in cardiac hypertrophy signal transduction regulation. Captopril throughs regulation GRK2 subcellular distribu

关 键 词：高血压 G蛋白偶联受体激酶2 心肌肥大 卡托普利 细胞信号转导 

分 类 号：R542.2[医药卫生—心血管疾病]