Effects of imipenem combined with low-dose cyclophosphamide on the intestinal barrier in septic rats

Anti-infection therapy combined with immunotherapy is one of the important research approaches for treating sepsis. However, the combination of anti-infection and immunotherapy therapeutic agents may have an adverse effect on intestinal barrier function. In the present study, it was hypothesized that imipenem combined with low-dose cyclophosphamide (CTX) could improve the sepsis survival rate compared with imipenem treatment alone. In addition, the alterations in the intestinal barrier were investigated and the possible mechanisms of altering intestinal barrier function in septic rats treated with imipenem combined with low-dose CTX or imipenem alone were explored. To investigate the effect of imipenem combined with low-dose CTX on the intestinal barrier, the markers of histopathology, intestinal permeability, intestinal epithelial apoptosis, cytokines interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α, and tight junction proteins zonula occludens (ZO)-1, occludin and claudin-2, were quantitatively and qualitatively evaluated. The results indicated that imipenem combined with low-dose CTX significantly improved the survival rate of rats compared with imipenem alone (P