Randomized Controlled Trial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2015; 21(7): 2183-2190
Published online Feb 21, 2015. doi: 10.3748/wjg.v21.i7.2183
MicroRNA profiling of the intestine during hypothermic circulatory arrest in swine
Wei-Bin Lin, Meng-Ya Liang, Guang-Xian Chen, Xiao Yang, Han Qin, Jian-Ping Yao, Kang-Ni Feng, Zhong-Kai Wu
Wei-Bin Lin, Meng-Ya Liang, Guang-Xian Chen, Xiao Yang, Han Qin, Jian-Ping Yao, Kang-Ni Feng, Zhong-Kai Wu, 2nd Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: Lin WB conducted the molecular studies, analyzed the data and drafted the manuscript; Chen GX, Liang MY and Yao JP participated in establishing the cardiopulmonary bypass model; Feng KN and Qin H participated in the design of the study and performed the statistical analysis; Wu ZK and Yang X conceived the study, participated in its design and coordination and helped to draft the manuscript; all authors read and approved the final manuscript.
Supported by National Basic Research Program of China (973 Program), No. 2010CB5295007; Pearl River Scholar Program, No. 80000-3210003; and Natural Science Fund of China, No. 81370215.
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: Zhong-Kai Wu, MD, PhD, 2nd Department of Cardiac surgery, the First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, Guangdong Province, China. wuzhk@mail.sysu.edu.cn
Telephone: +86-20-87755766 Fax: +86-20-87750632
Received: May 31, 2014
Peer-review started: June 1, 2014
First decision: July 21, 2014
Revised: August 12, 2014
Accepted: September 5, 2014
Article in press: September 5, 2014
Published online: February 21, 2015
Processing time: 255 Days and 21.8 Hours
Abstract

AIM: To perform a profiling analysis of changes in intestinal microRNA (miRNA) expression during hypothermic circulatory arrest (HCA).

METHODS: A total of eight piglets were randomly divided into HCA and sham operation (SO) groups. Under general anesthesia, swine in the HCA group were subjected to hypothermic cardiopulmonary bypass at 24 °C followed by 80 min of circulatory arrest, and the reperfusion lasted for 180 min after cross-clamp removal. The counterparts in the SO group were only subjected to median sternotomy. Histopathological analysis was used to detect mucosal injury, and Pick-and-Mix custom miRNA real-time polymerase chain reaction (PCR) panels containing 306 unique primer sets were utilized to assay unpooled intestinal samples harvested from the two groups.

RESULTS: The intestinal mucosa of the animals that were subjected to 24 °C HCA exhibited representative ischemic reperfusion injury of grade 2 or 3 according to the Chiu score. Such intestinal mucosal injuries, with the subepithelial space and epithelial layer lifting away from the lamina propria, were accompanied by shortened and irregular villi. On the contrary, the intestinal mucosa remained normal in the sham-operated animals. In total, twenty-five miRNAs were differentially expressed between the two groups (15 upregulated and 10 downregulated in the HCA group). Among these, eight miRNAs (miR-122, miR-221-5p, miR-31, miR-421-5p, miR-4333, miR-499-3p, miR-542 and let-7d-3p) were significantly dysregulated (four higher and four lower). The expression of miR-122 was significantly (5.37-fold) increased in the HCA group vs the SO group, indicating that it may play a key role in HCA-induced mucosal injury.

CONCLUSION: Exposure to HCA caused intestinal miRNA dysregulation and barrier dysfunction in swine. These altered miRNAs might be related to the protection or destruction of the intestinal barrier.

Keywords: Reperfusion injury; Cardiopulmonary bypass; Animal model; Barrier function; Randomized controlled trial; MicroRNA

Core tip: Swine intestine was subjected to hypothermia, cardiopulmonary bypass and ischemia/reperfusion following hypothermic circulatory arrest (HCA). These factors caused barrier dysfunction, resulting in gastrointestinal complications. Histopathological and microRNA (miRNA) array analyses were used to investigate the effects of HCA on the gut barrier. HCA was found to disturb barrier function in the small intestine and influence the miRNA levels in swine. Our results contribute to the body of research examining gut barrier function following HCA in vivo.