低分子量肝素对兔创伤感染时凝血功能障碍的预防作用

Preventive effect of low molecular weight heparin on coagulative disturbance in rabbits with trauma infection

目的采用撞击伤合并注入内毒素（LPS）的方法，建立实验性高凝状态的动物模型，探讨用低分子量肝素或氨甲环酸后的保护作用。方法采用BIM-Ⅱ型水平式生物撞击机撞击兔胸部，并静脉注入LPS，形成创伤合并LPS的致伤因素。实验用32只新西兰兔分为四组：创伤合并LPS对照组（对照组）、低分子量肝素治疗组（L组）、氨甲环酸治疗组（TA组）、合并用药组（L＋TA组）。用酶联免疫法测定IL-1B、IL-6含量的变化；采用发色底物chromozymP法测定抗凝血酶Ⅲ（AT-Ⅲ）活性；用血凝分析仪测定纤维蛋白原含量；用发色底物法测定组织因子（TF）、组织因子途径抑制物（TFPI）活性的变化。实验动物24h后留取肺、肾组织，进行病理学观察。结果对照组在创伤和注射LPS后，AT-Ⅲ活性明显下降，纤维蛋白原含量升高，TF及TFPI活性升高。肾脏中有微血栓形成。与对照组比较，L组IL—1β、IL-6的含量降低；TF在血浆中的活性降低，TFPI活性增高，TF／TFP1比值降低；脏器中微血栓的形成减少。TA组IL-1β、IL-6的含量低于对照组、但高于L组；TF、TFPI在血浆中的活性低于对照组和L组，TF／TFPI比值高于L组；肺动脉血栓形成，重要脏器血栓形成增加。L＋TA组IL-1β、IL-6的含量低于L组；TF活性低于对照组和L组，但TFPI活性高于对照组和L组，TF／TFPI比值低于L组；未见肺动脉血栓发生和重要脏器微血栓形成的增多。结论低分子量肝索除了抗凝之外，还可抑制炎症反应，降低TF的释放，减轻凝血反应；在已用低分子量肝素基础上用氨甲环酸，不会造成血栓形成，而单用氨甲环酸则相反。实验研究结果可为临床诊断和预防创伤、感染诱发的高凝状态提供理论和实验依据。

Objective To investigate the preventive effect of low molecular weight heparin or tranexamic acid in the rabbits with hypercoagulation induced by impact injury and intravenous infusion of the endotoxin. Methods Combination of impact injury and endotoxin was created by strike on rabbit chest with type BIM-Ⅱ biological impact machine and injection of endotoxin via vein. Thirty-two male New Zealand rabbits were divided into four groups in a completely random design as follows ： impact injury combined with endotoxin without treatment group （control group） , treatment with low molecular weight heparin （L group）, treatment with tranexamic acid （TA group）, and treatment with low molecular weight heparin and tranexamic acid （L ＋ TA group）. The changes of interleukin-1β （IL-1β） and interleukin-6 （IL-6） were observed by using the enzyme-linked immunosorbent assay; changes of antithrombin-m （AT-m） activity, tissue factor （TF） and tissue factor pathway inhibitors （TFPI） were detected by the chromogenic substrate method chromozym P; the content of fibrinogen was observed by coagulation analyzer. The lung and kidney were removed from the experimental animals at 24 hours post impact injury for histopathologic observation. Results In the control group, the activity of AT-Ⅲ was decreased obviously, while the content of fibrinogen and the activity of TF and TFPI were increased, with formation of the thrombosis in the kidney after injection of PLS. Compared with control group, the activity of TF and the content of IL-1β and IL-6 were reduced but the TFPI was increased in the L group, which resulted in a decrease of TF/TFPI ratio, with decrease of formation of the micro-thrombosis in the organs. The content of IL-1β and IL-6 in the TA group were reduced, which was still higher than that in the L group. In the TA group, the activity of TF and TFPI was lower than that in the L group and control group, with higher TF/TFPI ratio than the L group. The frequency of thrombosis increased in pulmonary artery and other im portant organs. The content of IL-1β and IL-6 in the L ＋ TA group was lower than that in the L group. In the L ＋ TA group, the activity of TF was lower than that in the L group and control group, but the activity of TFPI was higher than that in the L group and control group, with lower TF/TFPI ratio than the L group. There found no increase of thrombus in the pulmonary arterial and other important organs. Conclusions Besides anticoagulation function, the low molecular weight heparin can inhibit the inflammation reaction, reduce the release of TF and attenuate the coagulation reaction. On the basis of treatment with low molecular weight heparin, application of the tranexamic acid will not lead to the formation of thrombus, but the only use of the tranexamic acid would have the contrary results. The results of the study provide a theoretical and experinaental basis for clinical diagnosis and prevention of hypercoagulation induced by injury and infection.