川芎挥发油预防动脉血栓形成的机理研究

Mechanism Study of Volatile Oil of CHUANXIONG RHIZOMA in Preventing Arterial Thrombosis

目的:本研究探讨川芎挥发油预防动脉血栓形成的机理。方法:取SD雄性大鼠,运用大鼠颈总动脉局部贴敷三氯化铁(FeCl_(3))联合腹腔注射脂多糖(LPS)探索内皮细胞损伤与炎症的发生在血栓形成中的交互作用。在此基础上评价川芎挥发油对该模型的预防作用;以电刺激诱导大鼠颈总动脉血栓形成以及角叉菜胶致小鼠尾部血栓形成的作用,进一步从体外探索川芎挥发油对血小板聚集的作用机理。结果:腹腔注射LPS可显著协同增强颈总动脉局部贴敷FeCl_(3)致血栓形成的效果,其最佳比例为腹腔注射LPS 3 mg/kg与9%FeCl_(3)颈总动脉局部贴敷。与正常对照组比较,LPS联合FeCl_(3)贴敷能明显促进大鼠颈总动脉血栓形成(P<0.05),延长活化部分凝血活酶时间(APTT)(P<0.01)、升高纤维蛋白原(FIB)浓度(P<0.01);与模型对照组比较,川芎挥发油可明显改善LPS联合FeCl_(3)诱导大鼠颈总动脉血栓形成血流量变化(P<0.05)、显著减少血栓质量、缩短血栓长度(P<0.01),明显减少血清中丙二醛含量、增加血清一氧化氮含量(P<0.05或P<0.01),缩短APTT、延长凝血酶时间TT(P<0.05或P<0.01),降低FIB浓度(P<0.05),明显延长电刺激诱导大鼠颈总动脉血栓形成时间(P<0.05或P<0.01),显著抑制角叉菜胶致小鼠尾部血栓形成(P<0.01),显著抑制花生四烯酸(AA)及二磷酸腺苷(ADP)诱导的血小板聚集(P<0.01)。结论:血管内皮细胞功能紊乱与局部炎症的发生在动脉血栓形成中具有协同增效作用。川芎挥发油可有效预防动脉血栓的形成,其作用机理可能与具有较好保护血管内皮细胞、抑制血管炎症反应、抑制血小板聚集有关,详细作用机理有待深入研究。

Objective:To study the mechanism of volatile oil of CHUANXIONG RHIZOMA(VOLCX)in preventing arterial thrombosis.Methods:Male SD rats were applied with ferric chloride(FeCl_(3))on carotid artery combined with intraperitoneal injection of lipopolysaccharide to explore the interaction between endothelial cells injury and inflammation in thrombosis.On this basis,the preventive effect of VOLCX on the model was evaluated.Electrical stimulation was used to induce thrombosis in the common carotid artery of rats,and carrageenan was used to induce tail thrombosis in mice,in order to further explore the mechanism of VOLCX on platelet aggregation in vitro.Results:Intraperitoneal injection of LPS significantly enhanced common carotid artery thrombosis induced by FeCl_(3).The optimal dosage of LPS was 3 mg/kg and the concentration of FeCl_(3) was 9%.Compared with control group,the thrombosis in common carotid artery of rats was significantly improved by LPS combined with FeCl_(3) application(P<0.05),the activated partial thromboplastin time(APTT)was prolonged(P<0.01),and the fibrinogen(FIB)concentration was increased(P<0.01).Compared with model group,VOLCX significantly improved blood flow(P<0.0),reduced the mass and length of thrombus(P<0.01),significantly decreased the serum malondialdehyde level,increased the serum nitric oxide level(P<0.05 or P<0.01),shorten the APTT,prolonged thrombin time(TT)(P<0.05 or P<0.01),and decreased the FIB concentration(P<0.05).The electrical stimulation-induced common carotid artery thrombosis time was significantly prolonged(P<0.05 or P<0.01),and the carrageenan-induced thrombosis in mice tail was significantly inhibited(P<0.01).Arachidonic acid(AA)-and ADP-induced platelet aggregation was significantly inhibited(P<0.01).Conclusion:Vascular endothelial cell dysfunction and inflammation have a synergistic enhancement effect on the arterial thrombosis.VOLCX exerts anti-thrombotic effect on common carotid artery thrombosis,and its mechanism may be related to the protection of vascular endothelial cells,andinhibition of inflammation and platelets aggregation.However,the detailed mechanism needs to be further explored.