Intestinal injury following liver transplantation was mediated by TLR4/NF-κB activation-induced cell apoptosis

Dong Dong Yuan, Xin Jin Chi, Yi Jin, Xi Li, Mian Ge, Wan Ling Gao, Jian Qiang Guan, Ai Lan Zhang, Zi Qing Hei

Research output: Contribution to journalArticle

Abstract

Intestinal motility and barriers are often impaired due to intestinal congestion during liver transplantation. Intestinal bacteria and enterogenous endotoxins enter into the blood stream or lymphatic system and translocate to other organs, which can result in postoperative multi-organ dysfunction (MODF) and systemic inflammatory reaction syndrome (SIRS) severely affecting patient survival. However, the mechanisms underlying liver transplantation-induced intestinal injury remain unclear and effective therapies are lacking. Thus, the present study investigated whether these effects were associated with endotoxin-mediated apoptosis. Rat autologous orthotopic liver transplantation (AOLT) models were established to observe dynamic intestinal injuries at different time-points following reperfusion. Changes in the levels of endotoxins and the primary receptor, toll-like receptor 4 (TLR4), as well as its downstream signaling molecule, nuclear factor-κB (NF-κB) were all determined. Finally, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were conducted to detect caspase-3 expression and intestinal cell apoptosis, respectively. AOLT resulted in significant pathological intestinal injury, with the most serious intestine damage apparent four or eight hours following reperfusion. Furthermore, the levels of endotoxins and inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, peaked during this time period and gradually decreased to the normal level. Notably, TLR4 and downstream NF-κB expression, as well as NF-κB-mediated caspase-3 activation and intestinal cell aapoptosis coincided with the intestinal pathological damage. Thus, the possible mechanism of post-liver transplantation intestinal injury was demonstrated to be associated with NF-κB activation-induced cell apoptosis.

Original languageEnglish (US)
Pages (from-to)1525-1532
Number of pages8
JournalMolecular Medicine Reports
Volume13
Issue number2
DOIs
StatePublished - Feb 2016

Keywords

  • Apoptosis
  • Endotoxin
  • Intestinal injury
  • Liver transplantation
  • Nuclear factor-κB
  • Toll-like receptor 4

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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  • Cite this

    Yuan, D. D., Chi, X. J., Jin, Y., Li, X., Ge, M., Gao, W. L., Guan, J. Q., Zhang, A. L., & Hei, Z. Q. (2016). Intestinal injury following liver transplantation was mediated by TLR4/NF-κB activation-induced cell apoptosis. Molecular Medicine Reports, 13(2), 1525-1532. https://doi.org/10.3892/mmr.2015.4719