肿瘤坏死因子单抗及一氧化氮抑制剂对脾切除小鼠内毒素攻击的治疗作用

The therapeutic effects of tumor necrosis factor monoclonal antibody and nitric oxide inhibitor on endotoxemia in splenectomized mice

目的：观察肿瘤坏死因子（ＴＮＦ）单抗及一氧化氮（ＮＯ）抑制剂对脾切除小鼠内毒素攻击的治疗效应。方法：采用小鼠脾切除后内毒素攻击模型。结果：相同剂量内毒素（５ｍｇ／ｋｇ）攻击后，无脾动物死亡率明显高于有脾动物（Ｐ＜０．０１）；注射内毒素后５ｍｉｎ给予ＴＮＦ单抗治疗组，无脾动物死亡率明显降低（Ｐ＜０．０１）。应用ＮＯ抑制剂Ｌ－ＮＭＭＡ２ｍｇ／ｋｇ时，无脾动物死亡率明显降低（Ｐ＜０．０５）；但采用５ｍｇ／ｋｇ治疗时，死亡率则明显增高。结论：脾切除后动物凶险性感染的本质可能与ＴＮＦ大量生成及过量释放有关。ＴＮＦ拮抗剂及适当剂量的ＮＯ抑制剂对无脾动物凶险性感染的预防及治疗是有益的。

Objective:The present study was performed to investigate the treatment effects of tumor necrosis factor (TNF) monoclonal antibody and nitric oxide inhibitor on endotoxemia in splenectomized mice.Methods:Mice were subjected to splenectomy followed by endotoxin challenge. Results:When 5 mg/kg endotoxin (E.coli O111B4 LPS) was given intravenously, we found that the mortality rate of splenectomized mice was significantly higher than that of nonsplenectomized mice (P<001). When the former group received antiTNF monoclonal antibody (3 mg/kg), the mortality rate was significantly decreased. Similarly, in splenectomized mice received 2 mg/kg LNMMA (an nitric oxide synthase inhibitor), the mortality rate was also decreased (P<005). However, in mice received 5 mg/kg LNMMA, the mortality rate was dramatically increased.Conclusion:It is suggested that treatment with anti-TNF antibody and suitable dose of NO synthase inhibitor may play an important role in preventing overwhelming postsplenectomy infection.