淫羊藿苷剂量对静脉血栓模型大鼠凝血功能、炎症因子及纤溶指标的影响

Effects of different doses of Icariin on coagulation function,inflammatory factors and fibrinolytic indexes of venous thrombosis model rats

目的观察淫羊藿苷对静脉血栓大鼠凝血功能、炎症因子及纤溶系统的影响,进一步明确其作用机制。方法将54只大鼠随机分为5组,假手术组(n=10)、血栓组(n=14)、低剂量淫羊藿苷组(n=10)、中剂量淫羊藿苷组(n=10)和高剂量淫羊藿苷组(n=10),采用静脉狭窄法复制深静脉血栓模型后,各药物组分别设下静脉注射10、20、40 mg/kg的淫羊藿苷溶液,给药时间点为造模后1、24、48、72 h。末次给药1 h后,检测各组大鼠血栓重量、血浆凝血功能指标、纤溶系统指标、炎症因子浓度,以及静脉血管组织NF-κB p65、VCAM-1、TF的mRNA与蛋白表达。结果与血栓组比较,不同剂量淫羊藿苷组血栓重量减少(P<0.05),血浆D-二聚体、纤溶酶原激活剂抑制剂-1、白细胞介素1β和肿瘤坏死因子α浓度降低(P<0.05),血浆部分凝血活酶时间、凝血酶原时间、凝血酶时间与组织型纤溶酶原激活剂浓度增加(P<0.05),静脉血管组织NF-κB p65、VCAM-1、TF的mRNA与蛋白表达均降低(P<0.05),并且具有一定的剂量依赖性,剂量越大效果越明显。结论淫羊藿苷可通过改善凝血指标、纤溶系统指标与炎症反应来抑制静脉血栓的形成,并且该作用可能与调节NF-κB p65信号通路有关。

Objective To observe the effects of icariin on coagulation function,inflammatory factors and fibrinolytic system in rats with venous thrombosis,and to further clarify its mechanism.Methods 54 rats were randomly divided into 5 groups:sham operation group(n=10),thrombus group(n=14),low-dose icariin group(n=10),medium-dose icariin group(n=10),and high-dose icariin group(n=10).Each drug group was intravenously injected with icariin solution of 10,20,40 mg/kg,respectively.The time points of administration were1,24,48,72 h after modeling.Thrombus weight,plasma coagulation function indexes,fibrinolytic system indexes,inflammatory factor concentration,and mRNA and protein expressions of NF-κB P65,VCAM-1 and TF in venous and vascular tissues of rats were detected 1 h after the last administration.Results Compared with the thrombus group,different doses of ICariin group decreased thrombus weight(P<0.05),plasma d-dimer,plasminogen activator inhibitor-1,interleukin 1βand tumor necrosis factorαconcentrations(P<0.05).The mRNA and protein expressions of NF-κB P65,VCAM-1 and TF in venous tissues were decreased with the increase of plasma partial thrombin time,prothrombin time,thrombin time and tissue plasminogen activator concentration(P<0.05),and the effect was more obvious with the increase of dose.Conclusion Icariin can inhibit venous thrombosis by improving coagulation parameters,fibrinolytic system parameters and inflammatory response,and this effect may be related to the regulation of NF-κB P65 signaling pathway.