重组人Ⅱ型肿瘤坏死因子受体–抗体融合蛋白对脂多糖诱导休克大鼠肠损伤的保护作用

观察注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白 (rhu TNFR: Fc) 对脂多糖 (LPS) 诱导的休克大鼠肠损伤的保护作用及其可能机制。SD大鼠随机分为对照组、rhu TNFR: Fc组、LPS组和rhu TNFR: Fc + LPS组, 监测各组大鼠平均动脉压 (MAP) 计算其死亡率, 检测血清中肿瘤坏死因子-α (TNF-α) 含量和活性; 观察小肠病理形态变化。结果表明, 对照组和rhu TNFR: Fc组大鼠全部存活, MAP无变化, TNF-α含量和活性均维持较低水平; LPS组大鼠死亡率为83%, TNF-α含量和活性明显高于对照组; rhu TNFR: Fc + LPS组大鼠死亡率33%, TNF-α含量升高, 其活性较LPS组明显降低, rhu TNFR: Fc还能降低LPS所致的MDA含量和MPO活性的升高并减轻LPS所致的肠病理性损伤。因此rhu TNFR: Fc对LPS诱导的休克大鼠的肠损伤有保护作用, 其机制可能主要是竞争性结合TNF-α, 减低TNF-α活性以及抗氧化作用。

Protective effects of rhu TNFR: Fc against the lipopolysaccharide induced intestinal damage of rats and its underlying mechanism

To investigate the protective effects of recombinant human tumor necrosis factor receptor Ⅱ: IgG Fc fusion protein (rhu TNFR: Fc) against the lipopolysaccharide (LPS) induced intestinal damage of rats and its underlying mechanism.  SD rats were randomly divided into four groups: control group, rhuTNFR: Fc group, LPS group and rhu TNFR: Fc + LPS group.  Mean arterial pressure (MAP) was continuously monitored and the mortality rates were assessed.  The levels of TNF-α and its bioactivity in the serum were assessed by ELISA and flow cytometry respectively.  Pathologic changes of intestinal tissue were observed by HE staining.  The rats of control and rhu TNFR: Fc group all survived with stable MAP, and the low level and bioactivity of TNF-α in the serum were maintained.  While 83% of the rats in LPS group died by 6 h with the levels and bioactivity of TNF-α increasing significantly.  In rhu TNFR: Fc + LPS group, the mortality rate of rats dropped to 33%.  The TNF-α level increased compared with control group but its bioactivity decreased significantly compared with LPS group.  The MPO activity and content of MDA decreased significantly.  The status of pathological  manifestation in the intestine was also ameliorated.  These data suggest that rhu TNFR: Fc could protect rats from the acute intestine injury induced by LPS through ablating the rise in serum TNF-α level and bioactivity as well as anti-oxidation.