Intestinal injury following liver transplantation was mediated by TLR4/NF-κB activation-induced cell apoptosis
| Autor: | Mian Ge, Yi Jin, Jian‑Qiang Guan, Xin‑Jin Chi, Zi‑Qing Hei, Xi Li, Ai‑Lan Zhang, Wan‑Ling Gao, Dong‑Dong Yuan |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
endotoxin Cancer Research Pathology medicine.medical_specialty medicine.medical_treatment toll-like receptor 4 nuclear factor-κB intestinal injury Biology Liver transplantation Biochemistry Proinflammatory cytokine 03 medical and health sciences Postoperative Complications Genetics medicine Animals Humans Molecular Biology liver transplantation Caspase 3 apoptosis NF-kappa B Articles Cell cycle Systemic Inflammatory Response Syndrome Rats Endotoxins Intestines Transplantation 030104 developmental biology Oncology Terminal deoxynucleotidyl transferase Apoptosis TLR4 Cancer research Molecular Medicine Tumor necrosis factor alpha |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2015.4719 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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