Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2015; 21(43): 12370-12380
Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12370
Magnesium isoglycyrrhizinate inhibits inflammatory response through STAT3 pathway to protect remnant liver function
Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao
Guang-Hua Tang, Hua-Yu Yang, Jin-Chun Zhang, Jin-Jun Ren, Xin-Ting Sang, Xin Lu, Shou-Xian Zhong, Yi-Lei Mao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, China
Author contributions: Mao YL and Yang HY designed the research; Tang GH, Yang HY, Ren JJ and Zhang JC performed the research; Sang XT, Zhong SX and Lu X contributed new reagents or analytic tools; Tang GH analyzed the data and wrote the paper.
Supported by a grant from the State Science and Technology Ministry, No. 2012BAI06B01.
Institutional review board statement: The study protocol was approved by the Ethics Committee of the Peking Union Medical College Hospital.
Institutional animal care and use committee statement: All animal experiments were reviewed and approved by the Ethics Committee of the Peking Union Medical College Hospital.
Conflict-of-interest statement: The authors have none to declare.
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: Yi-Lei Mao, MD, PhD, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and PUMC, No. 1 Shuaifuyuan, Wangfujing, Beijing 100730, China. yileimao@126.com
Telephone: +86-10-69156042 Fax: +86-10-69156043
Received: May 4, 2015
Peer-review started: May 5, 2015
First decision: June 3, 2015
Revised: June 18, 2015
Accepted: September 14, 2015
Article in press: September 15, 2015
Published online: November 21, 2015
Abstract

AIM: To investigate the protective effect of magnesium isoglycyrrhizinate (MgIG) on excessive hepatectomy animal model and its possible mechanism.

METHODS: We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond’s method, in which the left, middle, right upper, and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups, and were injected intraperitoneally with 3 mL saline (control group), 30 mg/kg (low-dose group) and 60 mg/kg (high-dose group) of MgIG, respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl endopeptidase, total bilirubin (TBil), direct bilirubin (DBil), total protein, albumin, blood glucose (Glu), hyper-sensitivity C-reactive protein, prothrombin time (PT), and thrombin time (TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines (IL-1, IL-6, IL-10, and iNOS) was analyzed by ELISA. STAT3 protein and mRNA were analyzed by Western blot and quantitative reverse-transcription PCR, respectively.

RESULTS: The high-dose group demonstrated a significantly prolonged survival time, compared with both the control and the low-dose groups (22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h, P = 0.018). There were significant differences among the groups in ALT, Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the MgIG treated groups than in the control group. Both Glu and PT levels were significantly higher in the MgIG treated groups than in the control group. At 12 h, ALT, AST, TBil, DBil and TT levels showed significant differences between the MgIG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group, the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10, and a decrease in IL-6. Both STAT3 protein and mRNA levels were significantly lower in the MgIG treated groups than in the control group at 6 h, 12 h, and 18 h after surgery.

CONCLUSION: High-dose MgIG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflammatory response through inhibition of the STAT3 pathway.

Keywords: Magnesium isoglycyrrhizinate, Excessive liver resection, Inflammation, Liver regeneration, STAT3

Core tip: Magnesium isoglycyrrhizinate (MgIG), a hepatocyte protective agent, has been shown to have the effects of anti-inflammation, liver cell membrane protection, and liver function improvement. We designed this study, by using the standard 90% hepatectomy model in rats, to clarify the liver protecting function of MgIG and its mechanism. We have researched postoperative survival time, hepatocyte regeneration, liver function, serum inflammatory cytokines, STAT3 protein and mRNA expression. The protective effect of MgIG in standard 90% hepatectomy is limited, which can prolong the survival time. This hepatoprotective effect was not mediated by increasing hepatocyte regeneration but rather by inhibiting the inflammatory response through inhibition of the STAT3 pathway.