水蛭联合淮山药对静脉血栓栓塞症大鼠的保护作用

Protective effect of leech combined with Huai Yam on venous thromboembolism in rats

目的通过复制静脉血栓栓塞症大鼠模型,探讨水蛭联合淮山药对静脉血栓栓塞症的保护作用。方法选取40只SD雄性大鼠按随机分成空白组、假手术组、模型组、低分子肝素组、水蛭淮山药组,药物干预后取血及栓塞血管段,采用全自动血凝仪检测血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT);采用ELISA法检测血浆D二聚体(D-Dimer)及栓塞血管内皮素(ET)、一氧化氮(NO);采用免疫组织化学检测栓塞血管组织纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物-1(PAI-1)、血管性血友病因子(vWF)。结果与模型组比较,低分子肝素组、水蛭淮山药组的大鼠血浆PT、APTT、D-Dimer明显减少(t分别=-11.84、-10.58、-10.37、-10.19、-16.45、-16.39,P均<0.05);与模型组比较,低分子肝素组、水蛭淮山药组的大鼠栓塞血管组织ET明显降低、NO明显增加(t分别=-5.50、-5.89、5.61、5.73,P均<0.05);与模型组比较,低分子肝素组和水蛭淮山药组的血管t-PA阳性细胞比率明显升高(t分别=22.83、24.74,P均<0.05),PAI-1、vWF阳性细胞比率明显降低(t分别=-12.50、-11.51、-57.63、-55.86,P均<0.05)。结论水蛭联合淮山药可以显著降低VTE大鼠血浆PT、APTT及D-Dimer,显著下调栓塞血管段组织中ET、PAI-1、vWF的表达量,显著上调NO及t-PA的表达量,从而改善肺栓塞;其作用机制可能与改善内皮功能、提高凝血与纤溶调节能力有关。

Objective To investigate the protective effect of leech combined with Huai Yam on venous thromboembo⁃lism by establishing venous thromboembolism rat model.Methods Forty male SD rats were randomly divided into blank group,sham operation group,model group,low molecular weight heparin group and leech Huai yam group.After drug in⁃tervention,blood and embolized vascular segments were collected.Plasma prothrombin time(PT)and activated partial thrombin time(APTT)were measured by automatic coagulation apparatus.Plasma D-Dimer(D-dimer),vascular endothe⁃lin(ET)and nitric oxide(NO)were detected by ELISA.Vascular tissue plasminogen activator(t-PA),plasminogen activa⁃tor inhibitor-1(PAI-1)and von Willebrand factor(vWF)were detected by immunohistochemistry.Results Compared with model group,the PT,APTT and D-Dimer in low molecular weight heparin group and leech Huai Yam group were significantly decreased(t=-11.84,-10.58,-10.37,-10.19,-16.45,-16.39,P<0.05).Compared with model group,ET and NO in embolized vascular tis⁃sue of rats in low molecular weight heparin group and leech Huai Yam group were significantly de⁃creased and significantly increased(t=-5.50,-5.89,5.61,5.73,P<0.05).Compared with model group,the ratios of t-PA positive cells in low molecular weight heparin group and leech Huai Yam group were significantly increased(t=22.83,24.74,P<0.05),while the ratios of PAI-1 and vWF positive cells were significantly decreased(t=-12.50,-11.51,-57.63,-55.86,P<0.05).Conclusion Leech combined with Huai Yam can significantly reduce PT,APTT and D-Dimer in plasma of VTE rats,significantly down-regulate the expression levels of ET,PAI-1 and vWF in embolized vascular seg⁃ments,and significantly up-regulate the expression levels of NO and t-PA,so as to improve pulmonary embolism.It is sug⁃gested that the mechanism may be related to the improvement of endothelial function and the ability of coagulation and fibri⁃nolytic regulation.