厄贝沙坦对雄性自发性高血压大鼠纤溶和凝血变异性的影响

Effects of irbesartan on fibrinolytic/hemostatic variables in early male spontaneously hypertensive rats

目的观察厄贝沙坦在降压的同时,对早期雄性自发性高血压大鼠纤溶和凝血的影响。方法 15 周龄雄性自发性高血压大鼠20只,随机分为2组,厄贝沙坦组给厄贝沙坦50 mg·kg-1·d-1,对照组以等量蒸馏水代替。同龄雄性Wistar Kyoto大鼠10只作正常血压对照。采用1步法检测血浆凝血酶原时间 (prothrombin time,PT),采用凝血酶法检测血浆纤维蛋白原(fibrinogen,FIB)含量,采用发色底物法检测血浆组织型纤溶酶原激活物活性(tissue activator of plasminogen activator activity,tPA:A)、纤溶酶原激活物抑制物活性(plasminogen activator-1 inlhibitor activity,PAI:A)和α2-纤溶酶抑制物活性(inhibitor of α2- fibrinolysin inhibitor activcty,α2-PI:A)。结果与正常血压组比较:自发性高血压对照组血浆FIB显著增高 (P<0．01),α2-PI:A显著降低(P<0．01)。自发性高血压对照组和厄贝沙坦组t-PA较正常血压组显著增高 (P<0．05)而PT和PAI:A无明显差异。厄贝沙坦组治疗3个月后血压和FIB较对照组明显降低(P<0．01), α2-PI:A显著增高(P<0．01)。结论早期雄性自发性高血压鼠血管内凝血与纤溶并存,提示已处于慢性过代偿弥散性血管内凝血的凝溶期,有血栓栓塞和(或)出血的危险性;厄贝沙坦能逆转自发性高血压慢性隐性弥散性血管内凝血所致的血栓前状态和动脉粥样硬化,改善已受损的凝血和纤溶系统,降低出血性和 (或)血栓栓塞性并发症的危险。

Objectives To examine the effects of irbesartan on plasma prothrombin time （PT）, fibrinogen （FIB）, tissue-type plasminogen activator activity （t-PA：A）, plasminogen activator inhibitor activity （PAI： A） and cq plasmin inhibitor activity （α2-PI：A） in spontaneously hypertensive rats （SHR）. Methods Thirty male SHRs with 15 week-old were divided into two groups （n=10,eaeh）, irbesaxtan （50 mg·kg^-1·d^-1） or equal volume of distilled water were administered by drinking respectively for three months. Ten agematched male Wistar Kyoto （WKY） rats were also received equal volume of distilled water by drinking. Plasma PT were determined with one-step means, plasma FIB were determined by means of thrombin and plasma t-PA：A, PAI：A and α2-PI：A were determined by means of color substrate. Results After three months treatment of irbesartan, the blood pressure （BP） in SHRs were significantly decreased （P〈0.01）. SHR group had significantly higher FIB （P〈0.01）, SHR group and irbesartan group had significantly higher t-PA：A （P〈0.05） as compared to healthy WKY rat control group, but had no significant effect on PT and PAI：A. SHR group had significantly lower α2-PI：A （P〈0.01）. As compared to SHR group,irbesartan group had significantly lower FIB （P〈0.01） and higher α2-PI：A （P〈0.01）. Conclusions Intravascular coagulation and fibfinolysis in male early SHRs is concurrent, which indicate that there are chronic disseminated intravscular coagulation （DIC） in male early SHRs, therefore, who are in danger of thromboembollsm and/or hemorrhage; The intervention of irbesartan could improve the impaired coagulative and fibfinolytic system, and may reduce the complication of hemorrhage and/or thromboembolism.