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

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 20 mg·kg^-1 BW 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 10 mg·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/dt_max）和最大下降速率（-dp/dt_max）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/dt_max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。

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

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 Sprague-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 Gα 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/dtmax in chronic heart failure group significantly decreased, and protein Gα q/11 expression, basic and stimulated phospholipase C activity significantly increased (P<0.01). The ±dp/dtmax in benazepril group was significantly lower than that in control but obviously higher than that in chronic heart failure group (P<0.05). Gα q/11 expression, basic and stimulated phospholipase C activity in benazepril 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.