缬沙坦和贝那普利对高血压大鼠纤溶功能的影响

The effects of Benazepril and Valsartan on fibrinolytic function in spontaneously hypertensive rats

目的:探讨在整体情况下肾素-血管紧张素系统(RAS)和纤溶系统的关系,为血管紧张素转换酶抑制剂(ACEI)及血管紧张素Ⅱ型受体阻滞剂(ARB)治疗血栓性疾病、预防心血管事件的发生提供理论基础。方法:21只自发性高血压大鼠(SHR)分为对照组、贝那普利(Ben)组和缬沙坦(Val)组,分别用Ben 10 mg/(kg·d)和Val 30 mg/(kg·d)对SHR进行干预5周,观察纤溶指标的变化。血浆和孵育液中纤维酶原激活物抑制剂(PAI-1)、组织型纤溶酶原激活物(t-PA)活性的测定采用发色底物法,心肌组织PAI-1 mRNA的表达采用RT-PCR方法半定量测定。结果:药物干预后,SHR大鼠主动脉条孵浴液中PAI-1活性下降,血浆PAI-1活性受到抑制,Val组、Ben组心肌组织PAI-1 mRNA的表达较SHR组分别下降50.32％、16.94％(P<0.01,<0.05),Val组心肌组织PAI-1 mRNA的表达也低于Ben组(P<0.01)。结论:RAS参与了纤溶系统功能的调节,其过程主要是通过血管紧张素Ⅱ1型受体促进PAI-1的合成与释放而实现的,Val、Ben具有改善大鼠纤溶功能参数指标,提高纤溶系统活性的作用。

Objective:To investigate the correlation between RAS and fibrinolysis and put forward theoretical basis for treatment and prevention against ischemic cardiovascular events with ACEI and ARB. Methods: Twenty-one 8-week old SHR were randomly divided into three groups ( n = 7). The first group (SHR) were received plain drinking water. The other two groups, (SHR+Ben) (SHR+Val), were received benazepril (10 mg/kg · day), valsartan (30 mg/kg · day) in drinking water respetively for 5 weeks. At the end of 5 th week, the experimental SHRs were anesthetized and blood samples were taken for studying the changes of plasma PAI-1 and tPA activity. The chest was opened, and the heart and thoracic aorta were rapidly removed. The hearts were frozen in liquid nitrogen and stored at -80℃ for PAI-1 mRNA expression by RT-PCR. The aorta were incubated for observing the effects of benazepril and valsartan on PAI-1 release in isolated aorta. Results: After 5 weeks treatment of benazepril and valsartan, the activities of plasma PAI-1 were lower and the PAI-1-mRNA expression of myocardial tissue in Val and Ben group, compacod with that in SHR grouf, was dereased to 50. 72%, 16. 94% ( P<0. 01,<0. 05) respectively, and the PAI-1 mRNA expression of myocorelial tissue in Val group was lower than that in Ben group( P <0. 01). Conclusion: These results indicales that the RAS takes part in the regulation of fibrinolytion and this procedure is mainly due of promoting the biosynthesis and releas the PAI-1 by angiotension A(Ⅰ) receplor. Val, Ben can improve the fibrinolitic function of rats and elevate its activity effect of fibrinolyiticls system.