抗肿瘤坏死因子单克隆抗体治疗脓毒症的用药时机实验研究

目的：通过对脓毒症小鼠的治疗过程，探讨抗肿瘤坏死因子单克隆抗体（Ｚ１２）在脓毒症治疗中的作用和用药时机。方法：脓毒症模型采用ＮＨ１雄性小鼠，腹腔注射Ｏ１１１Ｂ４大肠杆菌１／２ＬＤ９０，共２次，间隔１２小时。给药分早期和晚期２组，分别于第１、２次细菌攻击时每鼠注射０．１ｍｇＺ１２。结果：早期使用抗Ｚ１２虽然可以降低血ＴＮＦ活性，但不能改善动物生存率，甚至有加速死亡的危险；晚期应用时生存率较早期用药时明显提高，与早期用药组有显著性差异（Ｐ＜０．０５）；白细胞计数Ｚ１２早期组和晚期组均低于生理盐水组，其中，晚期用药组有显著性差异（Ｐ＜０．０５）。Ｚ１２能够降低ＴＮＦ的活性水平，与生理盐水组比较，有显著性差异（Ｐ＜０．０５或Ｐ＜０．０１）。早期用Ｚ１２组血ＴＮＦ和ＩＬ６低于晚期用Ｚ１２组，有显著性差异（Ｐ均＜０．０５）；ＩＬ１则相反，早期组高于晚期组（Ｐ＜０．０５）。结论：Ｚ１２可以成为脓毒症治疗的辅助药物，关键是用药时间，其应用时机可能在感染的中后期，而不是早期

An animal experiment on timing of antitumor necrosis factor monoclonal antibody treatment in sepsis

Objective:To investigate the efficacy of antitumor necrosis factor (TNF) monoclonal antibody (Z12) administrated at different times in the treatment of septic mice.Methods:NH1 male mice were intraperitoneally challenged with a bolus injection of E.coli O 111 B 4 suspension twice at 12hour intervals.Z12 in a dose of 0 1 mg per mouse was intraperitoneally injected at first challenge (early treatment group) and at second challenge (delayed treatment group) respectively,and control group received the same volume (0 5 ml) of normal saline.Survival rate,white blood cell (WBC) counts of peripheral blood and cytokine activities were determined.Results:Survival rate in delayed treatment group was significantly higher than that in early treatment group ( P <0 05).Both early and delayed Z12 groups showed lower WBC and blood cytokine activities compared with the controls.Also,TNF and IL6 levels were markedly reduced in early group compared with delayed group (both P <0 05).However, IL1 activity in early group was significantly higher than that in delayed group ( P <0 05).Conclusions:AntiTNF antibody should be used at delayed stage rather than early stage after infection.