Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2016; 22(16): 4136-4148
Published online Apr 28, 2016. doi: 10.3748/wjg.v22.i16.4136
Recombinant adenovirus containing hyper-interleukin-6 and hepatocyte growth factor ameliorates acute-on-chronic liver failure in rats
Dan-Dan Gao, Jia Fu, Bo Qin, Wen-Xiang Huang, Chun Yang, Bei Jia
Dan-Dan Gao, Jia Fu, Bo Qin, Wen-Xiang Huang, Chun Yang, Bei Jia, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Author contributions: Jia B, Yang C, Qin B, Gao DD and Huang WX conceived and designed the study; Gao DD performed the experiments and wrote the paper; Fu J provided the mutants; Jia B and Gao DD analysed the data; and Jia B reviewed and edited the manuscript. Yang C and Jia B made equal contributions to this work.
Supported by Natural Science Foundation of Chongqing, No. cstc2012jjA10052; and Young High-End Medical Reserve Personnel Training Plan Foundation of Chongqing, China.
Institutional review board statement: The study was reviewed and approved by Chongqing Science and Technology Committee with protocol number cstc2012jjA10052.
Institutional animal care and use committee statement: All of the procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Ethical Committee on Animal Experiments at First Affiliated Hospital of Chongqing Medical University (Chongqing, China) with the reference number 2015-3.
Conflict-of-interest statement: The authors declare no conflict of interest.
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: Bei Jia, PhD, Chongqing Key Laboratory of Infectious Diseases and Parasitic Diseases, Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yu Zhong District, Chongqing 400016, China. beijia7410@163.com
Telephone: +86-23-89012427 Fax: +86-23-89012430
Received: November 25, 2015
Peer-review started: November 26, 2016
First decision: December 30, 2015
Revised: February 1, 2016
Accepted: March 1, 2016
Article in press: March 2, 2016
Published online: April 28, 2016
Processing time: 145 Days and 14.6 Hours
Abstract

AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF).

METHODS: The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or Ad-HGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological indexes.

RESULTS: Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1 (HMGB1), endotoxin, tumour necrosis factor (TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. Likewise, reduced hepatic damage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGF-HIL-6 treatment groups, more predominantly in the latter group.

CONCLUSION: This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects.

Keywords: Acute-on-chronic liver failure; Recombinant adenovirus; Hyper-interleukin-6; Hepatocyte growth factor; Inflammatory cytokines

Core tip: The purport of our study was to analyse the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF). In summary, our results suggest that Ad-HGF-HIL-6 may confer a more powerful protective effect against ACLF than do Ad-HGF or Ad-HIL-6 in rats and can restrain the secretion of diverse inflammatory cytokines and reduce the apoptosis of hepatocytes. Ad-HGF-HIL-6 is likely to be a feasible protective therapy for serious liver injury.