抗凝血酶-Ⅲ对多器官功能障碍综合征大鼠细胞因子的影响

Effects of antithrombin-Ⅲ on cytokines in rats with multiple organ dysfunction syndrome

目的观察抗凝血酶(AT)对多器官功能障碍综合征(MODS)大鼠细胞因子的影响。方法Wistar大鼠70只随机分为3组:正常对照组(n=10)、模型组(n=30)和AT治疗组(n=30)。经股静脉注射脂多糖(LPS)2次(100μg/kg和200μg/kg)制备大鼠全身炎症反应综合征(SIRS)/MODS动物模型。AT治疗组在第2次LPS攻击后1h股静脉注射AT25U/kg(0.5ml/100g)。正常对照组和模型组注射等量生理盐水。4h后取血测定内毒素(ET)、白细胞介素1(IL1)、IL6和肿瘤坏死因子α(TNFα)含量,同时取肺、肾、肝组织进行组织病理学观察。结果模型组动物血清ET、IL1、IL6和TNFα水平均明显升高(P均<0.01)。AT治疗后血清ET、IL1、IL6和TNFα水平均明显下降,与模型组比较差异均有显著性(P均<0.01),但仍显著高于正常对照组(P<0.05或P<0.01);肺、肾、肝组织的病理学变化较模型组明显减轻。结论AT能够拮抗炎症反应,对SIRS/MODS具有治疗作用。

Objective To observe the effect of the antithrombin -Ⅲ（AT-Ⅲ） on cytokine levels in multiple organ dysfunction syndrome （MODS） in rats. Methods Seventy Wistar rats were randomly divided into three groups： normal control group, MODS group, and AT-Ⅲ treatment group. The rats in MODS group and the treatment group were given lipopolysaccharide （LPS） two times to replicate systemic inflammatory response syndrome （SIRS）/MODS model. One hour after the injections of LPS, the rats in the treatment group were given AT-Ⅲ（25U/kg, 0.5ml/100g） intravenously. Four hours after treatment, blood samples were collected in rats. The tissue samples were collected and preserved in formalin. By use of radioimmunoassay and histopathology, the effect of the AT - Ⅲ was observed in rats with SIRS/MODS. Results Endotoxin （ET）, interleukin - 1 （IL-1） ,IL-6 and tumor necrosis factor-α（TNF-α） levels were all increased significantly in MODS animals （all P〈0. 01）, and they were decreased after AT - Ⅲ treatment （all P〈0.01）, though still higher than those of the normal controls （all P〈0.01）. The pathologic changes in lung, kidney,and liver in the treatment group were milder than in the MODS group. Conclusion These data suggest that AT-Ⅲ could inhibit systemic inflammatory response and it might be used in the treatment of SIRS/MODS.