Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2017; 23(40): 7242-7252
Published online Oct 28, 2017. doi: 10.3748/wjg.v23.i40.7242
Dachaihu decoction ameliorates pancreatic fibrosis by inhibiting macrophage infiltration in chronic pancreatitis
Li-Fang Duan, Xiao-Fan Xu, Lin-Jia Zhu, Fang Liu, Xiao-Qin Zhang, Nan Wu, Jian-Wei Fan, Jia-Qi Xin, Hong Zhang
Li-Fang Duan, Lin-Jia Zhu, Fang Liu, Xiao-Qin Zhang, Nan Wu, Jian-Wei Fan, Jia-Qi Xin, Hong Zhang, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China
Xiao-Fan Xu, Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China
Author contributions: Zhang H designed the research; Duan LF and Xu XF contributed equally to the work, and both performed most of the experiments and wrote the paper; Zhu LJ, Wu N, Fan JW and Xin JQ performed the experiments; Zhang XQ and Liu F analyzed the data.
Supported by the National Natural Science Foundation of China, No. 81673816; the Key Basic Research Project of Shaanxi Province, No. 2017ZDJC-14; and the Key Research Program of Natural Science of Shaanxi Education Department, No. 15JS027.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of the Shaanxi University of Chinese Medicine, Xianyang, China.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
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: Hong Zhang, MD, PhD, Professor, Department of Pathophysiology, Shaanxi University of Chinese Medicine, Shiji Avenue, Xianyang 712046, Shaanxi Province, China. zhangh1227@163.com
Telephone: +86-29-38183453 Fax: +86-29-38183453
Received: July 31, 2017
Peer-review started: August 19, 2017
First decision: September 6, 2017
Revised: September 22, 2017
Accepted: September 29, 2017
Article in press: September 26, 2017
Published online: October 28, 2017
Processing time: 71 Days and 4.2 Hours
Abstract
AIM

To explore the role of macrophages in chronic pancreatitis (CP) and the effect of Dachaihu decoction (DCHD) on pancreatic fibrosis in mice.

METHODS

KunMing mice were randomly divided into a control group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine (3 g/kg twice 1 d/wk for 6 wk). Mice in the DCHD group were administered DCHD intragastrically at a dose of 14 g/kg/d 1 wk after CP induction. At 2 wk, 4 wk and 6 wk post-modeling, the morphology of the pancreas was observed using hematoxylin and eosin, and Masson staining. Interleukin-6 (IL-6) serum levels were assayed using an enzyme-linked immunosorbent assay. Double immunofluorescence staining was performed to observe the co-expression of F4/80 and IL-6 in the pancreas. Inflammatory factors including monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and IL-6 were determined using real time-polymerase chain reaction. Western blot analysis was used to detect fibronectin levels in the pancreas.

RESULTS

Compared with the control group, mice with 20% L-arginine-induced CP had obvious macrophage infiltration and a higher level of fibrosis. IL-6 serum concentrations were significantly increased. Double immunofluorescence staining showed that IL-6 and F4/80 were co-expressed in the pancreas. With the administration of DCHD, the infiltration of macrophages and degree of fibrosis in the pancreas were significantly attenuated; IL-6, MCP-1 and MIP-1α mRNA, and fibronectin levels were reduced.

CONCLUSION

The dominant role of macrophages in the development of CP was mainly related to IL-6 production. DCHD was effective in ameliorating pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas.

Keywords: Dachaihu decoction; Pancreatic fibrosis; Macrophages; Interleukin-6

Core tip: Macrophages, important inflammatory cells, can also promote fibrogenesis by interfering with the synthesis and degradation of the extracellular matrix, as confirmed in both liver fibrosis and renal fibrosis models. Our study suggested that macrophages also play an important role in the development of pancreatic fibrosis. We found that macrophages are an important source of interleukin-6, which is involved in the progression of chronic pancreatitis (CP). Dachaihu decoction (DCHD), a traditional Chinese medicinal formula, effectively improves the clinical symptoms of CP patients, but the underlying mechanism remains unclear. We found that DCHD ameliorates pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion.