叶下珠有效部位对血栓形成的影响及其作用机制初探

采用Born方法和改良的Hamburger方法分别测定叶下珠 (Phyllanthusurinaria)含corilagin的有效部位 (代号PUW )在体内外对血小板聚集功能和对血小板与中性粒细胞之间粘附反应的影响 ;应用Myers方法评价PUW灌胃对小鼠尾静脉注射花生四烯酸 (AA)引起猝死的保护作用 ;运用改良的Charl ton方法及陈长勋等方法分别观察PUW灌胃对电刺激大鼠颈动脉血栓形成和下腔静脉血栓形成的影响 ;采用Tomihisa方法 ,观察PUW对大鼠尾尖出血时间的影响。结果显示 ,PUW在体内外对ADP、AA或血小板活化因子 (PAF)诱导的血小板聚集均无明显抑制作用 ;PUW呈浓度依赖性明显阻抑AA激活的血小板与中性粒细胞之间的粘附反应 ,其半数抑制浓度 (IC50 )为 39 7mg/kg。PUW (10、2 0和 4 0mg/kg)灌胃呈剂量依赖性显著减少AA致小鼠死亡的数量 ,明显延长电刺激大鼠颈动脉血栓形成时间 ,减轻大鼠下腔静脉血栓的干、湿重。 2 0mg/kg的PUW对出血时间无明显影响 ,4 0mg/kg的PUW虽延长出血时间 ,但与阿司匹林 (2 0mg/kg)比较 ,出血时间明显缩短 (P <0 0 5 )。本实验结果提示 ,PUW灌胃在多种体内血栓模型中均具有明显的抗血栓形成作用 ,其机制可能与阻抑血小板和中性粒细胞之间的的粘附作用密切相关。

Effects of the fraction from Phyllanthus urinaria on thrombosis and its mechanism

Born's and modified Hamburger's methods were used to determine the effects of PUW(effective fraction containing 60% corilagin from Phyllanthus urinaria ) on platelet aggregation and platelet leukocyte adhesion,respectively.The protective effect of PUW against the mouse sudden death was observed by use of Myers'method;the effects of PUW were evaluated on electrically stimulated rat carotid arterial thrombosis and rat inferior vena cave thrombosis according to the methods of Charlton and Chen Changxun,respectively.Tomihisa's method was used to investigate the influence of PUW on bleeding time.The results showed that PUW had no effect on ADP ,arachidonic acid(AA) ,or platelet activating factor induced platelet aggregation, in vitro or in vivo .PUW concentration dependently inhibited the binding of AA stimulated platelets to leukocytes with the medium inhibitory concentration of 39.7 mg/kg.Intragastric PUW significantly suppressed the mouse mortality,markedly prolonged the occlusion time,and decreased the wet and dry thrombus weight,in a dose dependent manner.20 mg/kg of PUW showed no significant influence on the bleeding time of rat tail tip.40 mg/kg of PUW prolonged the bleeding time whereas the bleeding time of PUW at 40 mg/kg was much shorter as compared with that of 20 mg/kg aspirin( P <0.05).The results suggested that PUW had significant protection against thrombus formation in the multiple thrombotic models.The mechanism might be closely related to its inhibition of platelet leukocyte adhesion.