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

Guo,Peng; Zhang,Shun‑Wen; Zhang,Jie; Dong,Jiang‑Tao; Wu,Jiang‑Dong; Tang,Su‑Tu; Yang,Jun‑Ting; Zhang,Wan‑Jiang; Wu,Fang

doi:10.3892/etm.2018.6373

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

Authors:
- Peng Guo
- Shun‑Wen Zhang
- Jie Zhang
- Jiang‑Tao Dong
- Jiang‑Dong Wu
- Su‑Tu Tang
- Jun‑Ting Yang
- Wan‑Jiang Zhang
- Fang Wu
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Affiliations: Department of Critical Care Medicine, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832000, P.R. China, First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China, Department of Emergency, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832000, P.R. China, Department of Neurosurgery, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832000, P.R. China, Department of Pathophysiology, Shihezi University School of Medicine/Key Laboratory of Xinjiang Endemic and Ethnic Diseases/Collaborative Innovation Center of High Incidence of Zoonotic Communicable Disease Prevention in the Western Region, Shihezi, Xinjiang 832000, P.R. China
Published online on: June 29, 2018 https://doi.org/10.3892/etm.2018.6373
Pages: 1919-1927
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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<0.05). However, no significantly difference between the treatment with imipenem combined with low‑dose CTX and imipenem treatment alone was indicated with regard to histopathology, intestinal permeability, intestinal epithelial apoptosis and the expression of claudin‑2, ZO‑1 and TNF‑α. However, imipenem combined with low‑dose CTX significantly reduced IL‑6 and IL‑10 expression and significantly increased occludin expression compared with imipenem alone (P<0.05). It was concluded that imipenem combined with low‑dose CTX could improve the survival rate of rats with sepsis compared with rats treated with imipenem alone. The present findings suggest that imipenem combined with low‑dose CTX may cause damage to the intestinal barrier function and the mechanism may be associated with a reduction in IL‑10 expression.

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