利伐沙班联合血栓通胶囊调控血栓调节蛋白表达抑制大鼠深静脉血栓形成的机制研究

Mechanism of Rivaroxaban Combined with Xueshuantong Capsules in Regulating Thrombomodulin Expression and Inhibit Deep Vein Thrombosis in Rats

目的研究利伐沙班联合血栓通胶囊对大鼠深静脉血栓的抑制作用。方法大鼠随机分为对照组、深静脉血栓模型组、利伐沙班组、血栓通胶囊组和利伐沙班联合血栓通胶囊组,每组12只。除对照组外,其余小鼠进行DVT造模。对照组和深静脉血栓模型组灌胃3 mL生理盐水;利伐沙班组灌胃2.6 mg/kg利伐沙班片;血栓通胶囊组灌胃0.45 g/kg血栓通胶囊;利伐沙班联合血栓通胶囊组灌胃2.6 mg/kg利伐沙班片和0.45 g/kg血栓通胶囊。连续给药7 d。观察凝血指标、血管内皮细胞组织、血栓质量,ELISA法和qRT-PCR检测TM、MCP-1、ICAM-1表达水平。结果与模型组、利伐沙班组和血栓通胶囊组相比,联合组APTT、PT、TT显著升高,FIB含量显著降低;血栓湿质量和干质量明显减少;TM、MCP-1、ICAM-1表达水平明显降低。内皮细胞组织切片显示联合组细胞结构损伤轻微,有极少炎症细胞附着(均P<0.05)。结论利伐沙班联合血栓通胶囊可提高血栓调节蛋白表达,抑制大鼠深静脉血栓损伤。

Objective:To study the inhibitory effect of rivaroxaban combined with Xueshuantong Capsules on deep vein thrombosis(DVT)in rats.Methods:Rats were randomly divided into the control group,deep vein thrombosis model group,Rivaroxaban group,Xueshuantong Capsules group and Rivaroxaban combined with Xuesh⁃uantong Capsules group,with 12 rats in each group.DVT modeling was performed in other rats except for the con⁃trol group.The control group and DVT model group were intragastrically injected with 3 mL normal saline.The Ri⁃varoxaban group was given 2.6 mg/kg of Rivaroxaban tablets intragastrically;the Xueshuantong Capsules group was intragastrically given 0.45 g/kg of Xueshuantong Capsules;Rivaroxaban combined with Xueshuantong Capsules group was intragastric given 2.6 mg/kg of Rivaroxaban tablets and 0.45g/kg of Xueshuantong Capsules.The drug was administered continuously for 7 days.The coagulation indicators,the vascular endothelial tissues and the thrombus qualities were detected.The expression levels of TM,MCP-1 and ICAM-1 were detected by ELISA and qRT-PCR.Results:Compared with model group,Rivaroxaban group and Xueshuantong Capsules group,the levels of APTT,PT and TT in combination group were significantly increased,while FIB content was significantly de⁃creased.The wet mass and dry mass of thrombus decreased obviously.The expression levels of TM,MCP-1 and ICAM-1 were significantly increased.Endothelial cell sections showed little structural damage and few inflammato⁃ry cells attached in the combination group(all P<0.05).Conclusion:Rivaroxaban combined with Xueshuantong Capsules can increase the expression of thrombomodulin and inhibit DVT injury in rats.