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

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

doi:10.3892/mmr.2015.4719

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

Authors:
- Dong‑Dong Yuan
- Xin‑Jin Chi
- Yi Jin
- Xi Li
- Mian Ge
- Wan‑Ling Gao
- Jian‑Qiang Guan
- Ai‑Lan Zhang
- Zi‑Qing Hei
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Affiliations: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Pathology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Thyroid and Breast Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: December 24, 2015 https://doi.org/10.3892/mmr.2015.4719
Pages: 1525-1532
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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