title: Intestinal injury following liver transplantation was mediated by TLR4/NF-κB activation-induced cell apoptosis.
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 apoptosis 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.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Xin-Jin
authors.initials: XJ
authors.lastname: Chi
authors.affiliation: Department of Pathology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Thyroid and Breast Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Mian
authors.initials: M
authors.lastname: Ge
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Ai-Lan
authors.initials: AL
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Zi-Qing
authors.initials: ZQ
authors.lastname: Hei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000096:biosynthesis; D004731:Endotoxins / Q000378:metabolism; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D011183:Postoperative Complications / Q000235:genetics / Q000473:pathology; D051381:Rats; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004731:Endotoxins; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D053148:Caspase 3