摘要
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.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2007年第5期862-864,共3页
Chinese Journal of Pathophysiology
基金
山东省卫生厅科研基金资助项目(No.2001CA2BFAB1)
关键词
心力衰竭
充血性
信号转导
Gq蛋白
磷脂酶C
苯那普利
Heart failure, congestive
Signal transduction
Gq protein
Phospholipase C
Benazepril