论文部分内容阅读
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。
AIM: To investigate the role of GRK2 in the development and progression of hypertensive cardiac hypertrophy and the effect of captopril on GRK2 expression, activity and subcellular distribution in myocardium. To investigate the effects of captopril Inhibition of cardiac hypertrophy mechanism. Methods: WKY (WKY), spontaneous hypertension (SHR, SHRA) rats, 8-month-old SHR (SHRB) and Cato Expression and distribution of GRK2 in left ventricular cardiomyocytes of Pulpal intervention SHR (SHRC group) rats. Results: The expression of GRK2 protein in left ventricular myocardium of rats in all groups showed no significant change (P> 0.05). The expression of GRK2 in cytoplasm was lower in SHRA group than in WKY group (P <0.01). The expression of GRK2 in SHRB group was lower than that in SHRC group (P <0.01), while the GRK2 expression in SHRC group was higher than that in SHRB group (P <0.05). The expression of GRK2 in SHRA group was higher than that in WKY group (P <0.01). The expression of GRK2 in SHRB group was higher than that in SHRA group (P <0.05), while the GRK2 expression in SHRC group was lower than SHRB group (P <0.01). No GRK2 expression in nucleoprotein. Confocal microscopy showed that GRK2 aggregated significantly in intercalated placenta of SHR rats, especially at the two ends of cardiomyocytes. Captopril decreased the distribution of GRK2 in the plasma membrane. CONCLUSIONS: GRK2 is closely related to the occurrence and development of cardiomyocyte hypertrophy and is involved in the regulation of cardiac myocyte signal transduction. Captopril exerts the inhibitory effect on cardiac hypertrophy by regulating GRK2 subcellular distribution.