不同剂量大黄苷元影响脑缺血大鼠血栓形成及血小板和凝血功能:与阿司匹林及尼莫地平的效应比较

Effect of different-dose rhubarb aglycone on thrombosis,platelet aggregation and adhesion,and blood coagulation in rats with cerebral ischemia:comparison with aspirin and Nimodipine

目的:观察不同剂量大黄及有效部位大黄苷元对脑缺血大鼠血栓形成和血小板功能及凝血功能的影响,并与标准药物阿斯匹林及尼莫地平相比较。方法:实验于2004-09/11在河南中医学院老年医学研究所实验室完成。选用84只SD雄性大鼠,随机分7组,12只/组。模型组、尼莫地平组10.8mg/(kg·d)、阿司匹林组20mg/(kg·d)、大黄苷元(由河南中医学院中药制剂教研室提供)25.92mg,51.84mg,103.68mg/(kg·d)组,阻塞大鼠大脑中动脉制备局灶性脑缺血模型。各用药组大鼠均于造模前4天开始灌胃,连续用药4d。假手术组和模型组分别用同等体积的生理盐水灌胃。术后测定神经症状、脑组织含水量、脑梗死面积、凝血功能(凝血酶原时间、凝血活酶时间、凝血酶时间、纤维蛋白原)、血小板聚集和黏附、血栓长度和湿重及干重。结果:84只大鼠在制备模型过程中死亡16只,进入统计分析大鼠68只。①各用药组较模型组大鼠神经症状评分、脑组织含水量、脑梗死面积均有显著降低(P<0.01),其中以大黄苷元25.92mg/(kg·d)组大鼠的神经症状评分降低尤为显著(P<0.01)。②各用药组大鼠血栓的长度、湿重、干重和血小板黏附率、聚集率均较模型组大鼠显著下降,其中以阿司匹林组和大黄苷元25.92mg/(kg·d)组血栓长度、湿重、干重的降低显著;大黄苷元25.92mg/(kg·d)组大鼠的血小板黏附率和聚集率均较阿司匹林组和尼莫低平组显著降低(P<0.01)。③各用药组大鼠的凝血酶原时间均较模型组大鼠延长(P<0.01),以阿司匹林组、尼莫低平组、大黄苷元51.84mg/(kg·d),25.92mg/(kg·d)组的延长明显;各用药组大鼠的纤维蛋白原均较模型组显著减少,以阿司匹林组、尼莫低平组、大黄苷元25.92mg/(kg·d)组大鼠纤维蛋白原的减少明显(P<0.01)。结论:大黄苷元能明显降低实验大鼠血栓重量和长度,具有显著的抗血栓形成的作用,能够减少纤维蛋白原,延长凝血时间,抑制血小板聚集和黏附的作用,以大黄苷元低剂量组作用更显著。

AIM:To study the effect of rhubarb aglycone on thrombosis,blood coagulation and platelet aggregation and adhesion in rats with cerebral ischemia and perform a comparison with the effect of aspirin and Nimodipine.METHODS:The experiment was finished in the Institute of Geriatrics, Henan College of Traditional Chinese Medicine from September to November 2004.Totally 84 SD male rats were divided randomly into seven groups(n=7):sham operation group,model group,Nimodipine group(10.8 mg/kg per day),aspirin group (20 mg/kg per day),low dosage of rhubarb aglycone group(25.92 mg/kg per day), middle dosage of rhubarb aglycone group (51.84 mg/kg per day),high dosage of rhubarb aglycone group(51.84 mg/kg per day).The focal cerebral ischemic model of cerebral middle artery occlusion was established.Rats in drug group received drugs 4 days before cerebral ischemia for consecutively 4 days.Rats in sham operation group and model group received the same dose of saline.The score of neural symptoms, the brain water content and the area of infarct,the length of thrombosis and the dry and wet weight, the ratio of platelet aggregation and adhesion, the function of blood coagulation(prothrombin time,thromboplastin time, thrombin time,fibrinogen) after operation.RESULTS:Among the 84 rats,16 died,and 68 were involved in the result analysis.①The score of neuron symptoms,the brain water content and the area of infarct in treated groups decreased significantly(P< 0.01).The score of neuron symptoms decreased most significantly in low dosage of rhubarb aglycone group(P< 0.01).②The length of thrombosis and the dry and wet weight,the ratio of platelet aggregation and adhesion in treated groups decreased obviously as compared with that in model group.The length of thrombosis and the dry and wet weight decreased most significantly in low dosage of rhubarb aglycone group and aspirin group;the ratio of platelet aggregation and adhesion in low dosage of rhubarb aglycone group decreased obviously as compared with that in aspirin and Nimodipine groups(P< 0.01).③The prothrombin time in treated groups was longer than that in model group(P< 0.01),which was prolonged obviously in aspirin,Nimodipine and low dosage of rhubarb aglycone groups.The fibrinogen in treated groups decreased obviously as compared with that in model group,which was decreased obviously in aspirin,Nimodipine and low dosage of rhubarb aglycone groups(P< 0.01). CONCLUSION:The rhubarb aglycone,especially the lowdose rbubarb aglycone,can decrease the length and weight of thrombosis, inhibit the thrombosis,decrease the fibrinogen and inhibit the blood coagulation and the aggregation and adhesion of platelet in experimental rats.