【作者】 杨娟；

【导师】 张莉蓉； 韩圣娜；

【作者基本信息】 郑州大学 ， 药理学， 2013， 硕士

【摘要】 研究背景与目的：延胡索乙素是从罂粟科植物延胡索中提取的一种生物碱。文献报道由于其有多重药理作用如镇痛、抗脑缺血、抗心律失常、抗心肌缺血等作用,长期以来一直广泛应用于临床实践中。本文重点从药效及机制方面研究延胡索乙素的抗血栓作用。第一部分：延胡索乙素体内药效研究目的：测定延胡索乙素体内抗血栓的效果。方法：将实验动物随机分为空白对照组、阿司匹林组(40mg·kg-1)、延胡索乙素组20mg·kg-1、40mg·kg-1、80mg·kg-1),各组动物连续灌胃7d,末次给药2h后建立各血栓模型测定延胡索乙素对血栓形成的影响。测定延胡索乙素对大鼠下腔静脉结扎致静脉血栓的影响；测定延胡索乙素对电刺激引起大鼠颈总动脉血栓模型和三氯化铁致大鼠颈总动脉血栓的影响；观察延胡索乙素对家兔非闭塞性静脉血栓、动静脉旁路模型、PT(凝血时间)和APTT(凝血酶原时间)测定及体内抗血小板聚集实验评价其抗血栓能力；观察延胡索乙素对家兔上皮流血时间和小鼠断尾流血时间的影响。结果：大鼠下腔静脉模型表明延胡索乙素有较好的抗血栓效果；大鼠电刺激模型实验表明延胡索乙素可有效减少动脉血栓形成,增加颈总动脉血流量(低中高剂量分别是空白组的1.6、1.9和2.1倍,且与空白组相比均P＜0.05)；延胡索乙素对三氯化铁损伤大鼠动脉内皮模型有明显的抑制作用(低中高剂量对血栓抑制率分别为8.6%、16.4%和32.8%)；并通过家兔体内血栓实验表明延胡索乙素有较好的抗血栓活性,且能有效延长PT和APTT和较好的抑制凝血酶和ADP诱导的血小板聚集；同时延胡索乙素高剂量延长流血时间,但与阳性对照无显著性差异(P＞0.05)。结论：延胡索乙素能抑制实验动物静脉血栓、动脉血栓和动静脉旁路血栓的形成。第二部分：机制研究目的：考察延胡索乙素抗血栓作用机制。方法：各组大鼠灌胃给药后,结扎大鼠髂静脉,正常饲养7天后,取结扎下方髂静脉血管,用免疫组化的方法测定血管内皮细胞的凋亡情况；测定大鼠体外ADP诱导的组织因子的表达情况。结果：延胡索乙素组与模型组有显著性差异(P＜0.01)。凋亡实验表明延胡索乙素能有效地抑制结扎后血管内皮细胞的凋亡,阿司匹林组抑制凋亡效果较差。PCR实验表明,阿司匹林对ADP诱导的组织因子表达没有抑制作用,而延胡索乙素能有效降低ADP诱导的组织因子表达。结论：延胡索乙素抗血栓作用与其抗损伤后的血管内皮凋亡和抑制组织因子表达有关。更多还原

【Abstract】 Background and ObjectivesTetrahydropalmatine is an alkaloid extracted from the poppy plants Corydalis. Tetrahydropalmatine has long been widely used in clinical practice because of its multiple pharmacological effects such as analgesic, anti-cerebral ischemia, antiarrhythmic and anti-ischemic effect which have been reported. This study focuses on the efficacy and mechanisms of tetrahydropalmatine antithrombotic effectPart1:Research on antithrombotic effect of TetrahydropalmatineMethodsWe further evaluated the antithrombotic effect of tetrahydropalmatne with more pharmacodynamic models. Antithrombotic activity in vivo was determined by causeing rat inferior vena cava ligation. Electrical stimulation induced carotid artery thrombosis model and FeC13induced rat carotid artery thrombosis model. Rabbit non-occlusive venous thrombosis model, arteriovenous shunt model, the PT and APTT and in vivo inhibition of platelet aggregation experiments to evaluate the ability of antithrombotic. Cuticle bleeding model bleeding time.ResultsThe rat inferior vena cava model showed a good antithrombotic effect. Rat electrical stimulation of the model experiments showed that the Tetrahydropalmatine was effective in reducing arterial thrombosis and increasing in carotid arterial blood flow. In the injured rats induced artery endothelial model by FeC13,also significantly inhibited (inhibition rates were8.6%,16.4%and32.8%respectively). And Tetrahydropalmatine can effectively prolong PT and APTT and inhibition of thrombin and ADP induced platelet aggregation.ConclusionTetrahydropalmatine has ovious effect on thrombosisformation and blood coagulation function.Part2:Research on mechanism of TetrahydropalmatineMethodsWe studied the mechanism of Tetrahydropalmatine antithrombotic effect. Vascular endothelial cell apoptosis was determined by immunohistochemical method. And determination of in vitro rat ADP and thrombin-induced tissue factor expression.ResultsApoptosis experiment indicated that tetrahydropalmatine can effectively inhibit the apoptosis after ligation of vessels, but aspirin did not inhibit of apoptosis. PCR results showed that Trimethylpyrazine inhibied tissue factor expression. And Tetrahydropalmatine could effectively reduce the ADP and thrombin-induced tissue factor expression.Conclusion:Tetrahydropalmatine-Antithrombotic effect iseffectively related to the resistance to vascular endothelial apoptosis and inhibition of tissue factor expression.更多还原