心力衰竭大鼠左室组织Gq蛋白-肌醇磷脂途径的变化及苯那普利的干预作用

Change of Gq-phosphoinositide signaling pathway in left ventricular tissue in rats with chronic heart failure and reverse effect of benazepril on it

目的:观察慢性心力衰竭大鼠左室组织中Gq蛋白-肌醇磷脂途径的变化,以阐明该信号转导通路在心力衰竭发病中的作用。方法:SD大鼠分为3组:对照组、心衰组和苯那普利干预组。心衰组大鼠腹腔注射阿霉素累积剂量达20mg.kg-1BW制作慢性心力衰竭模型,苯那普利组大鼠腹腔注射阿霉素同时给予苯那普利10mg.kg-1.d-1。4周后大鼠经颈内动脉插管至左心室行血流动力学测定,心肌组织中Gαq/11蛋白表达采用Western印迹法,磷脂酶C活性测定采用酶水解同位素底物法。结果:心衰组大鼠左室压力最大上升速率(+dp/dtmax)和最大下降速率(-dp/dtmax)均显著低于对照组,其左室组织中Gαq/11蛋白表达、基础磷脂酶C活性和GTPγS刺激后磷脂酶C活性均显著高于对照组(P<0.01)。苯那普利组大鼠±dp/dtmax均显著低于对照组但高于心衰组(P<0.05),其左室组织中Gαq/11蛋白表达、基础磷脂酶C活性和GTPγS刺激后磷脂酶C活性均显著低于心衰组但高于对照组(P<0.01)。结论:心力衰竭大鼠左室组织中Gq蛋白-肌醇磷脂途径活性显著升高,该信号通路的过度活化可能在心衰的发生中起到一定的作用,ACEI类药物苯那普利可部分逆转心衰大鼠左室组织中Gq蛋白-肌醇磷脂途径的激活。

AIM ： To investigate the changes of Gq - phosphoinositide pathway in left ventricular tissue of rats with chronic heart failure in order to assess the role of this signal pathway in the formation of heart failure. METHODS： Male Spragne - Dawle rats were divided into three groups： control, chronic heart failure and benazepril therapy group. Chronic heart failure was induced with adriamycin. Rats in benazepril group received benazepril 10 mg·kg^-1·d^-1 and adriamycin at the same time. Hemodynamic measurement was carried out after 4 weeks. The expression of Get q/11 protein in left ventricle was detected by Western blotting analysis and activity of phospholipase C was measured by the method of hydrolysis of nuclear substrate. RESULTS： Compared with control group, the ＋ dp/dtmax in chronic heart failure group significantly decreased, and protein Get q/11 expression, basic and stimulated phospholipase C activity significantly increased （P 〈0. 01 ）. The ＋ dp/dtmax in benazepril group was significantly lower than that in control but obviously higher than that in chronic heart failure group （P 〈 0. 05 ）. Get q/11 expression, basic and stimulated phospholipase C activity in benazepfil group were significantly higher than those in control but obviously lower than those in heart failure group （P 〈 0. 01 ）. CONCLUSION： Gq -phosphoinositide signaling pathway may play a role in the formation of chronic heart failure. Benazepril partialy attenuates the activation of phosphoinositide signaling pathway.