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[摘要]
目的 观察注射用血塞通(冻干)对电刺激所致家兔下腔静脉血栓形成的影响,并对其作用机制进行探讨。方法 使用电刺激伴狭窄法制备家兔下腔静脉血栓模型,造模1 h后,连续5天iv给予5、10、20 mg/kg的注射用血塞通(冻干)、sc给予100 U/kg的低分子肝素钠注射液,最后一次给药1 h后测定家兔出血时间和出血量,颈动脉取血分离血浆,试剂盒法检测活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)以及纤维蛋白原(FIa)水平,ELISA试剂盒法检测血浆内凝血因子FIIa、FXa、FXIa、抗凝血酶III(ATIII)、凝血因子TAT、活化蛋白C(APC)、组织性纤维溶酶激活剂(t-PA)、纤溶酶原(PLG)、尿激酶原(PROUK)、胰蛋白酶(Trypsin)、6-酮前列腺素F1a(6-keto-PGF1a)和血栓素B2(TXB2)水平;取血栓,测定血栓湿质量、干质量以及基质量。在血小板聚集实验中,制备家兔贫、富血小板血浆,分别以胶原(CG)、二磷酸腺苷二钠盐(ADP)和花生四烯酸钠(AA)为诱导剂,比浊法测定不同浓度血塞通对血小板聚集的影响。结果 家兔iv注射用血塞通(冻干)后,与模型组比较,血栓湿质量、干质量及基质量均显著降低,并具有一定的剂量依赖性;出血时间和出血量未出现明显增加,APTT、PT和TT也未出现明显变化;血浆内t-PA和6-keto-PGF1a水平显著增加,TXB2水平显著降低,其他指标没有明显变化。在血小板聚集实验中,血塞通可以剂量依赖性地抑制由AA诱导的血小板聚集。结论 注射用血塞通(冻干)具有良好的抑制下腔静脉血栓作用,且无明显出血副作用,作用机制与增强纤溶活性、抑制血小板聚集和血管收缩有关。
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[Abstract]
Objective To study the inhibitory effect of Xuesaitong Injection (freeze-drying) on inferior vena cava thrombosis in rabbits, observe its bleeding side effect and its effect on coagulation function, and explore its mechanism. Methods Inferior vena cava thrombosis model in rabbits was created by electrical stimulation and stenosis. One hour later, Xuesaitong Injection (freeze-drying) of 5, 10, and 20 mg/kg were injected into ear vein of rabbits for 5 d after surgery, and low molecular weight heparin sodium injection of 100 U/kg was sc given as a positive drug. Bleeding time and blood loss were measured 1 h after infusion. Blood was taken from the jugular vein and prepared into plasma. Activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and fibrinogen (FIa) were determined by kits, and coagulation factor FIIa, FXa, FXIa, antithrombin III (ATIII), coagulation factor TAT, activated protein C (APC), tissue fibrinolytic enzyme activator (t-PA), plasminogen (PLG), prourokinase (PROUK), trypsin, 6-keto-PGF1a, and thromboxane B2(TXB2) were determined by enzyme immunoassay kit. Thrombus was taken out, and wet weight, dry weight and base quality of thrombus were determined. In the platelet aggregation experiment, platelet-poor and platelet-rich plasma were prepared, and collagen (CG), ADP, and arachidonic acid (AA) were used as the inducers. Effects of different concentration of Xuesaitong Injection (freeze-drying) on platelet aggregation were measured using nephelometry. Results Wet weight, dry weight, and base quality of thrombus were all significantly reduced in a dose-dependent manner after injection of Xuesaitong Injection (freeze-drying), which indicated that Xuesaitong Injection (freeze-drying) had a significant inhibitory effect on deep vein thrombosis. After administration of Xuesaitong Injection(freeze-drying), bleeding time and blood loss of rabbits were no significant extended, and APTT, PT, and TT did not change significantly compared with the model group, which indicated that Xuesaitong Injection (freeze-drying) showed no significant bleeding side effects when it played antithrombotic effect. After administration of Xuesaitong Injection (freeze-drying), t-PA and 6-keto-PGF1a in rabbit plasma were significantly increased, and TXB2 was significantly reduced. In the platelet aggregation experiment, Xuesaitong Injection (freeze-drying) could inhibit platelet aggregation induced by AA in a dose dependent manner. Conclusion Xuesaitong Injection (freeze-drying) has a good inhibitory effect on inferior vena cava thrombosis, and its mechanism of action may be related to enhancing fibrinolysis and inhibition of platelet aggregation and vasoconstriction.
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[基金项目]
天津市应用基础与前沿技术研究计划青年项目(14JCQNJC13300)