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©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
AIM
To investigate the effect of ischaemia and reperfusion (I/R) injury on the Ca2+-ATPase activation in the intestinal tissue of a rat autologous orthotopic liver transplantation model and to determine if hypoxia preconditioning (HP) therapy induces HIF-1α to protect rat intestinal tissue against I/R injury.
METHODS
Rats received non-lethal hypoxic preconditioning therapy to induce HIF-1α expression. We used an autologous orthotopic liver transplantation model to imitate the I/R injury in intestinal tissue. Then, we detected the microstructure changes in small intestinal tissues, Ca2+-ATPase activity, apoptosis, and inflammation within 48 h postoperatively.
RESULTS
HIF-1α expression was significantly increased in intestinal tissue at 12 h postoperatively in rats that were exposed to a hypoxic environment for 90 min compared with a non-HP group (HP vs AT, P = 0.0177). Pathological analysis was performed on the intestinal mucosa cells, and the cells in the HP group appeared healthier than the cells in the AT group. The Ca2+-ATPase activity in the small intestinal cells in the AT group was significantly lower after the operation, and the Ca2+-ATPase activity in the HP group recovered faster than that in the AT group at 6 h postoperatively (HP vs AT, P = 0.0106). BCL-2 expression in the HP group was significantly higher than that in the AT group at 12 h postoperatively (HP vs AT P = 0.0010). 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.
CONCLUSION
Hypoxia-induced HIF-1α could protect intestinal mucosal cells against mitochondrial damage after I/R injury. HP could improve hypoxia tolerance in small intestinal mucosal cells and increase Ca2+-ATPase activity to reduce the apoptosis of and pathological damage to intestinal cells. HP could be a useful way to promote the earlier recovery of intestinal function after graft procedure.
Core tip: Ischaemia/reperfusion (I/R) injury affects the recovery of postoperative bowel function in liver transplantation. In our research, hypoxia-induced HIF-1α expression could protect mitochondrial function and Ca2+-ATPase activity against I/R injury to reduce the apoptosis and pathological damage to intestinal cells. Therefore, we suggest that hypoxic preconditioning therapy could improve the tolerance of small intestinal mucosal cell to hypoxia in rat autologous orthotopic liver transplantation.
