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.