可溶性TNFR-Fc融合蛋白对大鼠MODS的保护作用

Protective effect of soluble tumor necrosis factor receptor-Fc fusion protein on multiple organ dysfunction syndrome in rats

目的 :观察肿瘤坏死因子 (TNF)及肿瘤坏死因子受体 (TNFR)与多器官功能障碍综合征 (MODS)的关系 ,探讨可溶性肿瘤坏死因子受体 - Fc融合蛋白 (s TNFRp75 - Fc)在 MODS中的保护效果及作用机制。 方法 :将 4 8只雄性 SD大鼠随机分为正常组、模型组、给药组 ,通过创伤 +感染二次打击 ,建立“双相迟发”大鼠 MODS模型 ,在模型基础上动物复苏时静滴 0 .4mg/ kg s TNFRp75 - Fc作为给药组。采用 Western印迹技术 ,对各组大鼠主要器官细胞膜表面 TNFR表达量进行分析。结果 :给药组动物主要器官损害指标明显减轻 (P<0 .0 5 ) ,MODS发生率 (4 3.7% )和病死率 (12 .5 % )与模型组 (10 0 .0 %、5 0 .0 % )相比均显著降低 (P<0 .0 5 )。s TNFRp75 - Fc显著抑制血浆中 TNF-α活性。正常组 TNFR1和 TNFR2均为低水平表达 ,MODS模型鼠的两种 TNFR表达较正常组明显增强 ;给予 s TNFRp75 - Fc后各器官中两种 TNFR水平均明显下降。结论 :TNF-α及TNFR的表达在 MODS的发生发展过程中起十分重要的作用 ,外源性 s TNFR的应用可能减少细胞膜 TNFR的表达。实验证明 s TNFRp75 - Fc可以对

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 α and TNFR play key roles in the pathogenesis of MODS and sTNFR could reverse the effects of TNF α and decrease the morbidity of MODS and the mortality of animals in MODS model.