抗凝血酶-Ⅲ对内毒素血症大鼠凝血功能异常的治疗作用

Treatment effects of antithrombin -Ⅲ on coagulation abnormalities in rats with endotoxaemia

目的探讨抗凝血酶-Ⅲ（AT-Ⅲ）对内毒素血症大鼠凝血功能异常的治疗作用。方法采用静脉注射革兰阴性菌脂多糖（LPS）复制大鼠内毒素血症凝血功能异常模型。24只Wistar大鼠随机分为正常对照组、凝血功能异常组和AT-Ⅲ治疗组，每组8只。采用连续2次股静脉插管注射LPS[1．4ml／kg（100pg）和2．8ml／kg（200μg），每次间隔12h]制备内毒素血症凝血功能异常模型。AT-Ⅲ治疗组在第二次注射LPS后1h经股静脉注射AT-Ⅲ25U／kg。3h后取血并处死大鼠，观察各组血小板计数（PLT）、活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、D-二聚体、AT-Ⅲ活性、纤维蛋自原（FI）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）和乳酸脱氢酶（LDH）的水平，取肺、肾、肝组织观察其病理学变化。结果凝血功能异常组大鼠PLT、FI和AT-Ⅲ均较正常对照组明显降低（P均〈0．01），APTT、D-二聚体、PT、ALT、AST、ALP和LDH则均较正常对照组显著升高（P均〈0.01）；A-Ⅲ治疗组各项指标均显著改善，接近正常对照组水平（P均〉0.05），与凝血功能异常组比较差异也均有显著性（P均〈0.01）。肺、肾、肝组织病理学检查结果显示，AT-Ⅲ治疗后，内毒素血症大鼠各器官组织病理学损伤程度明显减轻。结论检测血中AT-Ⅲ水平对内毒素导致的弥散性血管内凝血（DIC）具有早期诊断的价值。在内毒素血症凝血功能障碍早期预防性使用AT-Ⅲ，对内毒素血症大鼠凝血功能异常有治疗作用。

Objective To study the treatment effects of antithrombin -Ⅲ （AT - Ⅲ ） on coagulation abnormalities in rats with endotoxaemia. Methods Twenty -four Wistar rats were randomly divided into control group, coagulation abnormality group and AT-Ⅲ group （each n=8）. Endotoxaemia coagulopathy model was reproduced by intravenous injection of lipopolysaccharide （LPS） in two doses of 1.4 ml/kg （100 μg）and 2.8 ml/kg （200 μg） 12 hours apart. In the AT- Ⅲ group, AT- Ⅲ 25 U/kg was given intravenously 1 hour after second injection of LPS. The changes in blood platelet （PLT） count, activated partial thromboplastin time （APTT）, prothrombin time （PT）, D-dimer （DD）, AT- Ⅲ activity, fibrinogen （FI）, alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）and lactate dehydrogenase （LDH） were determined 3 hours later. Results Levels of PLT, FI and AT -Ⅲ in coagulation abnormality group were lowered compared with control group （all P〈0. 01）, while APTT, DD, PT, ALT, AST, ALP and LDH were increased （all P〈0. 01）. All indexes were significantly improved in AT-Ⅲ group, the values were close to those of normal control group （all P〈0. 05）, and the differences were significant when compared with those of coagulation abnormality group （all P〈0. 01）. Pathological changes of the lung, kidney and liver tissues were lighter in AT - Ⅲ group than those of coagulation abnormality group. Conclusion These findings indicate that AT -Ⅲ can be used to treat disseminated intravascular coagulation （DIC） in rats with endotoxaemia. Preventive use of AT - Ⅲ in rats with endotoxaemia is therapeutically effective.