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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Acanthopanax senticosus polysaccharides-induced intestinal tight junction injury alleviation via inhibition of NF-κB/MLCK pathway in a mouse endotoxemia model
Jie Han, Ji-Hong Li, Guang Bai, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Shuo Wang, Xian-Jun Liu
Jie Han, Guo-Shun Shen, Jing Chen, Jia-Nan Liu, Xian-Jun Liu, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China
Ji-Hong Li, Department of Pharmacy, Affiliated Hospital, Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China
Guang Bai, Department of Gastroenterology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China
Shuo Wang, Testing and Analysis Center, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China
Author contributions: Han J and Liu XJ conceived and designed the experiments; Han J, Li JH, Liu JN and Wang S performed the experiments; Bai G provided proposal of intestinal damage; Shen GS and Chen J statistically analyzed the data; Han J wrote the manuscript; Liu XJ reviewed the manuscript; all authors have read and approved the final manuscript.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, China, Protocol No. SYXK (Liao) 2011-0001.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
Data sharing statement: The data referred to in this manuscript have been generated solely by the authors. No other party has been involved. Therefore, no additional unpublished data are available.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: Xian-Jun Liu, PhD, Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenhe District, Shenyang 110866, Liaoning Province, China. synydoctor@163.com
Telephone: +86-24-88487156 Fax: +86-24-88487156
Received: December 9, 2016
Peer-review started: December 11, 2016
First decision: January 10, 2017
Revised: January 18, 2017
Accepted: February 16, 2017
Article in press: February 17, 2017
Published online: March 28, 2017
AIM
To examine the effects of Acanthopanax senticosus polysaccharides (ASPS) on intestinal tight junction (TJ) disruption and nuclear factor-kappa B (NF-κB)/myosin light chain kinase (MLCK) activation in endotoxemia.
METHODS
BALB/C mice (6-8-weeks-old) received continuous intragastric gavage of ASPS for 7 d before injection of lipopolysaccharide (LPS), or received ASPS once after LPS injection. Blood and intestinal mucosal samples were collected 6 h after LPS challenge. Clinical symptoms, histological injury, intestinal permeability, TJ ultrastructure, and TJ protein expression were determined.
RESULTS
Compared with mice in the LPS group, pretreatment with ASPS improved clinical and histological scores by 390.9% (P < 0.05) and 57.89% (P < 0.05), respectively, and gut permeability change in endotoxemic mice was shown by a 61.93% reduction in reduced leakage of fluorescein isothiocyanate-dextran 6 h after LPS injection (P < 0.05). ASPS pretreatment also prevented LPS-induced TJ ultrastructure breakdown supported by increased electron dense materials between adjoining cells, sustained redistribution and expression of occludin (0.597 ± 0.027 vs 0.103 ± 0.009, P < 0.05) and zonula occludens-1 (0.507 ± 0.032 vs 0.125 ± 0.019, P < 0.05), and suppressed activation of the NF-κB/MLCK pathway indicated by reduced expression of NF-κB, phospho-inhibitor kappa B-alpha, MLCK and phospho-myosin light-chain-2 by 16.06% (P < 0.05), 54.31% (P < 0.05), 66.10% (P < 0.05) and 64.82% (P < 0.05), respectively.
CONCLUSION
ASPS pretreatment may be associated with inhibition of the NF-κB/MLCK pathway and concomitant amelioration of LPS-induced TJ dysfunction of intestinal epithelium in endotoxemia.
Core tip:Acanthopanax senticosus polysaccharides (ASPS) effectively protect against gastric tight junction (TJ) injury in sepsis. ASPS pretreatment significantly improved intestinal histological appearance and gut permeability, increased electron dense between adjoining cells, sustained the expression and redistribution of occludin and zonula occludens-1, suppressed the expression of nuclear factor-kappa B p65 (NF-κBp65) and phospho-inhibitor kappa B-alpha and myosin light chain kinase (MLCK), as well as phospho-myosin light-chain-2 in endotoxemia. These findings suggest that ASPS pretreatment may be associated with inhibition of the NF-κB/MLCK pathway and concomitant amelioration of gastric TJ dysfunction in the mouse model of endotoxemia.
