Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2015; 21(35): 10104-10112
Published online Sep 21, 2015. doi: 10.3748/wjg.v21.i35.10104
Effects of salvianolic acid B on liver mitochondria of rats with nonalcoholic steatohepatitis
Ying-Chun Wang, Wei-Zong Kong, Qing-Mei Jin, Juan Chen, Lei Dong
Ying-Chun Wang, Lei Dong, Department of Gastroenterology, the Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Ying-Chun Wang, Wei-Zong Kong, Qing-Mei Jin, Juan Chen, Department of Gastroenterology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning Province, China
Author contributions: Wang YC designed the research, analyzed the data and wrote the paper; Kong WZ performed the majority of research; Jin QM and Chen J performed the research; Dong L designed the research and provided fund support.
Institutional review board statement: The study was reviewed and approved by The Second Affiliated Hospital of Xi’an Jiaotong University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Dalian Medical University (IACUC protocol number: SCXK (Liao) 2013-0003).
Conflict-of-interest statement: The authors declare that there is no conflict 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: Lei Dong, MD, Professor, Department of Gastroenterology, the Second Affiliated Hospital, Xi’an Jiaotong University, No. 157 Siwu Road, Beida Street, Xi’an 710004, Shaanxi Province, China. dong556@126.com
Telephone: +86-29-87679750 Fax: +86-29-876798758
Received: January 10, 2015
Peer-review started: January 10, 2015
First decision: March 13, 2015
Revised: April 25, 2015
Accepted: June 15, 2015
Article in press: June 15, 2015
Published online: September 21, 2015
Processing time: 250 Days and 11.8 Hours
Abstract

AIM: To investigate the effects of salvianolic acid B (Sal B) on the morphological characteristics and functions of liver mitochondria of rats with nonalcoholic steatohepatitis (NASH).

METHODS: A total of 60 male Sprague-Dawley rats were randomly divided into three groups: (1) a normal group fed a normal diet; (2) an NASH model group; and (3) a Sal B-treated group fed a high-fat diet. Two rats from each group were executed at the end of the 12th week to detect pathological changes. The rats in the Sal B-treated group were gavaged with 20 mL/kg Sal B (1 mg/mL) daily. The model group received an equal volume of distilled water as a control. At the end of the 24th weekend, the remaining rats were executed. Serum biochemical parameters and liver histological characteristics were observed. Malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver were determined. Protein expression of CytC and caspase-3 was determined by immunohistochemistry. The mRNA transcripts of mitofusin-2 (Mfn2) and NF-κB in the liver tissue were detected by real-time PCR. Mitochondrial membrane potential was detected using a fluorescence spectrophotometer. Mitochondrial respiratory function was detected using a Clark oxygen electrode.

RESULTS: The model group showed significantly higher ALT, AST, TG, TC and MDA but significantly lower SOD than the normal group. In the model group, the histological characteristics of inflammation and steatosis were also evident; mitochondrial swelling and crest were shortened or even disappeared. CytC (18.46 ± 1.21 vs 60.01 ± 3.43, P < 0.01) and caspase-3 protein expression (30.26 ± 2.56 vs 83.31 ± 5.12, P < 0.01) increased significantly. The mRNA expression of NF-κB increased (0.81 ± 0.02 vs 0.91 ± 0.03, P < 0.05), whereas the mRNA expression of Mfn2 decreased (1.65 ± 0.31 vs 0.83 ± 0.16, P < 0.05). Mitochondrial membrane potential also decreased and breathing of rats was weakened. Steatosis and inflammation degrees in the treatment group were significantly alleviated compared with those of the model group. In the treatment group, mitochondrial swelling was alleviated. CytC (60.01 ± 3.43 vs 30.52 ± 2.01, P < 0.01) and caspase-3 protein expression (83.31 ± 5.12 vs 40.15 ± 3.26, P < 0.01) significantly decreased. The mRNA expression of NF-κB also decreased (0.91 ± 0.03 vs 0.74 ± 0.02, P < 0.01), whereas the mRNA expression of Mfn2 increased (0.83 ± 0.16 vs 1.35 ± 0.23, P < 0.01). Mitochondrial membrane potential increased and respiratory function was enhanced.

CONCLUSION: Sal B can treat NASH by protecting the morphological characteristics and functions of liver mitochondria, regulating lipid metabolism, controlling oxidative stress and lipid peroxidation and inhibiting apoptosis.

Keywords: Nonalcoholic steatohepatitis; Salvianolic acid B; Apoptosis; Liver; Mitochondria

Core tip: This study applied salvianolic acid B (Sal B) as intervention for rats with nonalcoholic steatohepatitis (NASH). We also observed the changes in biochemical indexes, mitochondrial morphological characteristics and functions and apoptosis index before and after Sal B treatment was administered to explore the pathogenesis of NASH and therapeutic effects of Sal B. Sal B can treat NASH by protecting the morphological characteristics and functions of liver mitochondria, regulating lipid metabolism, controlling oxidative stress and lipid peroxidation and inhibiting apoptosis.