Immunoglobulin preparations attenuate organ dysfunction and hemostatic abnormality by suppressing the production of cytokines in lipopolysaccharide-induced disseminated intravascular coagulation in rats
Immunoglobulin preparations attenuate organ dysfunction and hemostatic abnormality by suppressing the production of cytokines in lipopolysaccharide-induced disseminated intravascular coagulation in rats
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DOI：
10.1097/01.ccm.0000230382.38989.4f
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发表时间：
2006-09-01
影响因子：
8.8
通讯作者：
Nakao, Shinji
中科院分区：
文献类型：
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作者：
Asakura, Hidesaku;Takahashi, Yoko;Nakao, Shinji
目的：我们试图阐明免疫球蛋白浓缩物对大鼠脂多糖（LPS）诱导的弥散性血管内凝血（DIC）模型的影响。设计：前瞻性、比较、实验研究。地点：大学医院实验室。受试者：雄性 Wistar 大鼠，年龄 6 至 7 周，体重 160 至 170 g。干预：进行两种实验。首先，通过尾静脉持续输注 30 mg/kg LPS 4 小时诱导实验性 DIC，并在输注 LPS 前 30 分钟给大鼠注射两剂免疫球蛋白（25 或 100 mg/kg/4.5 小时），之后继续输注免疫球蛋白 4 小时。第二个实验中，通过持续输注（5 mg/kg/1 小时）LPS 1 小时来诱导实验性 DIC，并在 LPS 诱导后向大鼠施用一剂免疫球蛋白（100 mg/kg/4 小时）。第一个实验中的参数是在 4 小时和 8 小时时估计的，第二个实验中的参数是在 1、5 和 10 小时时估计的。 测量和主要结果： 在两个实验中观察到类似的结果。消耗性凝血障碍和止血活性均减弱，尤其是在输注 LPS 之前施用免疫球蛋白时。联合给予免疫球蛋白可显着降低肌酐和丙氨酸转氨酶的血浆水平。在 LPS 诱导的 DIC 模型中观察到明显的肾小球纤维蛋白沉积，但免疫球蛋白可减少这种沉积。在实验的第一阶段，肿瘤坏死因子（TNF）和白细胞介素（IL）-6的血浆水平通过免疫球蛋白的共同施用被抑制。第二，免疫球蛋白显着抑制血浆IL-6水平。结论：在LPS诱导的DIC模型中，免疫球蛋白可显着抑制血浆TNF和IL-6水平。此外，免疫球蛋白可改善该模型中的止血异常、器官功能障碍和肾小球纤维蛋白沉积。
Objective: We attempted to clarify the effect of immunoglobulin concentrates on the rat lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) model.Design: Prospective, comparative, experimental study.Setting: Laboratory at a university hospital.Subjects: Male Wistar rats, aged 6 to 7 wks and weighing 160 to 170 g.Interventions: Two kinds of experiments were performed. In the first, experimental DIC was induced by sustained infusion of 30 mg/kg LPS for 4 hrs via the tail vein, and two doses of immunoglobulin (25 or 100 mg/kg/4.5 hrs) were administered to rats 30 mins before infusion of LPS, after which immunoglobulin infusion was continued for a further 4 hrs. In the second, experimental DIC was induced by sustained infusion (5 mg/kg/1 hr) of LPS for 1 hr, and one dose of immunoglobulin (100 mg/kg/4 hrs) was administered to rats after LPS induction. The parameters were estimated at 4 hrs and 8 hrs in the first experiment and at 1, 5, and 10 hrs in the second one.Measurement and Main Results: Similar results were observed in the two experiments. Consumption coagulopathy and hemostatic activation were attenuated, especially when immunoglobulin was administered before LPS infusion. Plasma levels of creatinine and alanine aminotransferase were significantly depressed by coadministration of immunoglobulin. Marked glomerular fibrin deposition was observed in the LPS-induced DIC model, but this deposition was reduced by immunoglobulin. In the first stage of the experiment, plasma levels of tumor necrosis factor (TNF) and interleukin (IL)-6 were suppressed by coadministration of immunoglobulin. In the second, plasma levels of IL-6 were significantly suppressed by immunoglobulin.Conclusion: It was concluded that plasma levels of TNF and IL-6 could be significantly suppressed by immunoglobulin in the LPS-induced DIC model. Moreover, hemostatic abnormality, organ dysfunction, and glomerular fibrin deposition in this model were all ameliorated by immunoglobulin.