Protective effect of soluble tumor necrosis factor receptor-Fc fusion protein on multiple organ dysfunction syndrome in rats / 第二军医大学学报

ABSTRACT

Objective: To investigate the relations among the levels of TNF,TNFR and the frequency of multiple organ dysfunction syndrome(MODS),and to study the possible effect of sTNFR Fc in the treatment of MODS. Methods: Totally 48 healthy male SD rats were randomly divided into the control group, the MODS model group and the sTNFR Fc group.MODS group were established by two hit. At the early stage of resuscitation, 0.4 mg/kg of sTNFRp75 Fc was administrated via vein as the sTNFR Fc group. Levels of TNFR1 and TNFR2 expression on the cell membrane of various organs in the 3 groups were analyzed by Western blot. Results: After administration of sTNFRp75 Fc, the functions of the main organs were obviously improved. The morbidity(43.7%) of MODS and the mortality(12.5%) of animals decreased significantly in the sTNFR Fc group compared with model group(100.0% and 50.0%). The serum TNF bioactivity was significantly blocked by TNFR Fc administration. Both TNFR1 and TNFR2 expression in the control group were low while higher in the MODS model group; however, they were decreased significantly in various organs after sTNFRp75 Fc treatment.Conclusion: Our results suggest that TNF ? and TNFR play key roles in the pathogenesis of MODS and sTNFR could reverse the effects of TNF ? and decrease the morbidity of MODS and the mortality of animals in MODS model.