免疫吸附清除肿瘤坏死因子对内毒素休克兔肾脏的作用

The effects of removing circulated TNF by immunoadsorption on renal changes in rabbits with endotoxin shock

应用抗肿瘤坏死因子（ＴＮＦ）单克隆抗体免疫吸附方法，特异性清除循环ＴＮＦ，观察对内毒素休克肾脏的作用。方法以致死剂量内毒素（８×１０９ｃｆｕ／ｋｇ）制成内毒素休克动物模型，１小时后开始体外循环免疫吸附，监测平均动脉压（ＭＡＰ）变化，循环ＴＮＦ及尿素氮（ＢＵＮ）、肌酐（Ｃｒ）水平。６小时后活杀动物，留取肾脏行组织病理检查。结果（１）免疫吸附组血液灌流后３０分钟ＭＡＰ开始回升（１１．６±１．４ｋＰａ），明显高于对照组（８．８±２．３ｋＰａ，Ｐ＜０．０１）；（２）免疫吸附组２小时的ＴＮＦ活性（４４±１０Ｕ／ｍｌ）较对照组（１４４８±２２６Ｕ／ｍｌ）明显降低（Ｐ＜０．０５）；血清ＢＵＮ、Ｃｒ水平较对照组降低（Ｐ＜０．０５）；（３）免疫吸附组肾小球充血，白细胞浸润及肾小管坏死程度和线粒体的损害均较对照组明显减轻。结论抗ＴＮＦ单克隆抗体特异性免疫吸附方法，能有效清除血循环ＴＮＦ。早期降低ＴＮＦ水平，有效地缓解内毒素休克时的低血压状态，减轻肾脏病理损害。

Objectives To remove circulating tumornecrosi factor(TNF)by specific immunoadsorption column containing anti TNF monoclonal antibody(McAb)and observe the effects of the therapy on renalchanges in experimental endotoxin shock.Methods New Zealand white rabbits were injected with lethal dose of E.coli endotoxin(LPS,8×10 9cfu/kg)to produce endotoxin shock,then were divid edinto two groups:control(n=7)and perfusion group(n=10).Perfusion was started at 1hour after administration of endotoxin.Mean arterial pressure(MAP)was monitored continuously.Blood sampl eswere collected for assay of TNF,urea nitrogen(BUN)and creatinin(Cr).Six hours after infusion of LPS,rabbits were sacrificed,then the kidney was taken for pathologic observation.Results MAP was increased 30 minutes after perfusion in perfusion group,then kept at a level higher than that in the control group in the monitoring period( P <0.01).The plasma TNF activation was reduced significantly in the perfusion group(44±10)compared with the control group(1448±226, P <0.05)one hour after perfusion.The levels of BUN and Cr were decreased in the perfusion group compared with the contr olgroup.The degree of glomerularcongestion and infiltration of leukocytes in glomeruli was significantlylower in the perfusion group than in the control group.The degree of tubular necrosis wasdecreased significantly in the perfusion group compared to that in the control group( P <0.05).The mitochondri alultrastructural changes were more severe in the controlgroup than in the perfusion group.Conclusions Specific immunoadsorptive column containing anti TNFMcAb could remove effectively circulating TNF in experimental endotoxin shock.Reducing levels of TNF in the early phase of endotox in shockmay ameliorate the state of hypotension.