Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2018; 24(3): 360-370
Published online Jan 21, 2018. doi: 10.3748/wjg.v24.i3.360
Hypoxia preconditioning protects Ca2+-ATPase activation of intestinal mucosal cells against R/I injury in a rat liver transplantation model
Zhi-Peng Ji, Yuan-Xin Li, Bao-Xu Shi, Zhuo-Nan Zhuang, Jing-Yan Yang, Sen Guo, Xiao-Zhou Xu, Ke-Sen Xu, Hai-Lin Li
Zhi-Peng Ji, Department of General Surgery, the Second Hospital of Shandong University, Jinan 250033, Shandong Province, China
Yuan-Xin Li, Zhuo-Nan Zhuang, Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
Bao-Xu Shi, Department of Neurology, People’s Hospital of Rizhaolanshan, Rizhao 276800, Shandong Province, China
Jing-Yan Yang, Department of Pathology, the Second Hospital of Shandong University, Jinan 250033, Shandong Province, China
Sen Guo, Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, Jinan 250033, Shandong Province, China
Xiao-Zhou Xu, Ke-Sen Xu, Hai-Lin Li, Department of Hepatobiliary Surgery, the Second Hospital of Shandong University, Shandong University, Jinan 250033, Shandong Province, China
Author contributions: Ji ZP and Li HL designed the research and drafted and revised the paper; Ji ZP and Zhuang ZN performed the research; Shi BX, Guo S, Xu XZ and Zhuang ZN searched the literature and analysed the data; Xu KS and Li HL revised the paper and approved the final version; Yang JY provided technical assistance with pathology analysis.
Supported by The Second Hospital of Shandong University Youth Foundation, No. Y2013010033.
Institutional review board statement: The study was reviewed and approved by The Second Hospital of Shandong University Institutional Review Board.
Conflict-of-interest statement: We declare that there are no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hai-Lin Li, MD, PhD, Adjunct Professor, Department of Hepatobiliary Surgery, the Second Hospital of Shandong University, Shandong University, 247#, Beiyuan Street, Jinan 250033, Shandong Province, China. lehaln01@163.com
Telephone: +86-531-82169203 Fax: +86-531-82169243
Received: October 17, 2017
Peer-review started: October 17, 2017
First decision: October 31, 2017
Revised: November 7, 2017
Accepted: November 27, 2017
Article in press: November 27, 2017
Published online: January 21, 2018
Processing time: 94 Days and 6.9 Hours
ARTICLE HIGHLIGHTS
Research background

During liver transplantation, intestinal ischaemia/reperfusion (I/R) injury usually occurs due to the blockage of blood flow in the portal vein. Intestinal mucosal I/R injury is related with SIRS and MODS after shock or trauma. The postoperative recovery of small intestinal mucosal cells is important in treatment and prognosis. Non-lethal hypoxic preconditioning (HP) can increase tolerance to I/R injury and is effective in reducing damage to a variety of organs. In our previous study, we induced HIF-1α expression in liver tissue by exposing rats to a non-lethal hypoxia environment, and detected changes in the NF-κB and Erk pathways. Moreover, changes in glucose metabolism were also detected, and hypoxia-induced HIF-1α expression promoted HK2 and Glut1 expression, which could decrease liver inflammation and I/R injury after orthotopic liver transplantation. BCL-2 is considered an important anti-apoptotic protein. Ca2+-ATPase damage is one of the early manifestations in intestinal mucosa cells during ischaemia-reperfusion injury.

Research motivation

In this study, we investigated how I/R injury affects the Ca2+-ATPase activation in intestinal tissue in a rat autologous orthotopic liver transplantation model.

Research objectives

To investigate the effect of I/R injury on the Ca2+-ATPase activation in rat intestinal tissue in a rat autologous orthotopic liver transplantation model and to determine if HP therapy induced HIF-1α to protect rat intestinal tissue against I/R injury.

Research methods

Non-lethal hypoxic preconditioning therapy was applied to induce HIF-1α expression. An autologous orthotopic liver transplantation model was established to imitate I/R injury to intestinal tissue. Then, we detected the microstructure changes in small intestinal tissues using histology and immunohistochemistry, the expression of HIF-1α, cleaved Caspase 3, and cleaved PARP by Western blot analysis, and the expression of inflammatory factors in rat serum by ELISA.

Research results

After HP therapy, HIF-1α expression was significantly increased in intestinal tissue of rats at 12 h postoperatively. Pathology of the intestinal mucosal cells appeared healthier in the HP group than in the AT group. The Ca2+-ATPase activity in small intestinal cells in the HP group recovered faster than that in the AT group. BCL-2 expression in the HP group was significantly higher than that in the AT group. The expression of the inflammatory factors NO, SOD, IL-6 and TNF-α was significantly lower in the HP group than in the AT group.

Research conclusions

Hypoxia-induced HIF-1α could protect against the I/R injury to mitochondria and preserve Ca2+-ATPase activity in rat intestinal tissue. HP can improve the tolerance of small intestinal mucosal cells to hypoxia, and reduce the apoptosis by increasing BCL2 expression and pathological damage to intestinal cells.

Research perspectives

Non-lethal HP could be a useful way to promote the earlier recovery of intestinal function after graft procedure.