2-(α-羟基戊基)苯甲酸钾盐对大鼠血小板聚集、PGI_2/TXA_2比值和纤溶系统活性的影响  

Dl-PHPB Inhibits Platelet Aggregation and Affects the Balance of PGI_2/TXA_2 and Fibrinolytic System of Rats

作　　者：杨宏艳[1,2] 王玲[1] 李江[1] 徐少锋[1] 王伟平[1] 彭英[1] 王晓良[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050 [2]齐齐哈尔医学院,黑龙江齐齐哈尔161006

出　　处：《中国药学杂志》2015年第12期1021-1025,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金面上项目(81373387);国家科技重大专项重大新药创制(2012ZX09301002-004)

摘　　要：目的观察2-(α-羟基戊基)苯甲酸钾盐对大鼠血小板聚集及前列环素/血栓素A2和纤溶系统的影响。方法大鼠随机分为正常对照组、2-(α-羟基戊基)苯甲酸钾盐(1.3、3.9、12.9 mg·kg-1)给药组和噻氯匹定组。2-(α-羟基戊基)苯甲酸钾盐静脉给药30 min后,腹主动脉取血,血小板聚集仪检测血小板聚集率,流式细胞术测定血小板表面CD62p的表达,放免法检测大鼠血浆血栓素B2和6-酮-前列腺素F1α含量,酶联免疫分析法检测组织型纤溶酶原激活剂和纤溶酶原激活物抑制物1的含量。结果 2-(α-羟基戊基)苯甲酸钾盐在对抗二磷酸腺苷、胶原、花生四烯酸和凝血酶4种诱导剂引起的血小板聚集中,可显著的、剂量依赖性的抑制二磷酸腺苷诱导的大鼠血小板聚集,降低血小板表面CD62p的表达,增加大鼠血浆前列环素代谢物6-酮-前列腺素F1α含量,对血栓素A2代谢物血栓素B2无影响,2-(α-羟基戊基)苯甲酸钾盐还明显减少纤溶酶原激活物抑制物1含量,不影响血浆中组织型纤溶酶原激活剂的含量。结论 2-(α-羟基戊基)苯甲酸钾盐可明显抑制二磷酸腺苷诱导的血小板聚集和活化,升高前列环素/血栓素A2比值,增强纤溶系统活性。OBJECTIVE To investigate the effect of potassiam 2-（ 1-hydroxypentyl）-benzoae（ dl-PHPB） on platelet aggregation,the balance of PGI2/ TXA2 and fibrinolytic system of rats. METHODS Rats were randomly divided into 5 groups： control group,low（ 1. 3 mg·kg- 1）,middle（ 3. 9 mg·kg- 1） and high（ 12. 9 mg·kg- 1） dose of dl-PHPB groups and ticlopidine group. Blood was taken from the abdominal aorta 30 min after dl-PHPB administrated intravenously,and the rate of platelet aggregation was detected by platelet aggregometer. The expression of CD62 p on the surface of platelet was determined by flow cytometry. The contents of 6-KetoPGF1α,thromboxane B2（ TXB2）,t-PA and PAI-1 in serum were measured by radio-immuno assay and ELISA kit,respectively.RESULTS dl-PHPB inhibited rat platelet aggregation induced by ADP in dose-dependent manner more potently compared with AA,collagen and thrombin. dl-PHPB also decreased the expression of CD62 p. It increased the level of 6-keto-PGF1α,the metabolite of prostaglandin I2（ PGI2） and reduced the content of PAI-1. But dl-PHPB had no effect on the contents of TXB2,the metabolite of TXA2 and t-PA. CONCLUSION dl-PHPB may significantly inhibit rat platelet aggregation induced by ADP,increase the ratio of PGI2/TXA2 and enhance the activity of fibrinolytic system.

关 键 词：2-(α-羟基戊基)苯甲酸钾盐 二磷酸腺苷 血小板聚集 血栓素A2 前列腺素I2 

分 类 号：R965[医药卫生—药理学]