Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2015; 21(9): 2651-2657
Published online Mar 7, 2015. doi: 10.3748/wjg.v21.i9.2651
Are gastric mucosal macrophages responsible for gastric injury in acute pancreatitis?
Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, De-Li Jiang, Rong-Fang Chen, Jian-Guo Qu, Xiang-Qian Shen, Min Chen, Min Gu
Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
De-Li Jiang, Min Chen, School of Chemistry and Chemical Engineering of Jiangsu University, Zhenjiang 212013, Jiangsu Province, China
Xiang-Qian Shen, Institute for Advanced Materials, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China
Min Gu, Zhengjang Integrative Medicine Hospital, Zhenjiang 212001, Jiangsu Province, China
Author contributions: Dang SC, Zhang JX and Gu M contributed equally to this work; Dang SC and Zhang JX designed the research; Dang SC, Wang H, Cui L, Chen RF, Qu JG and Shen XQ performed the research; Jiang DL and Chen M prepared the liposomes; Dang SC analyzed the data; Dang SC and Gu M wrote the paper.
Supported by Jiangsu Planned Projects for Postdoctoral Research Funds, No. 1302096B; and Natural Science Foundation of Jiangsu Province, No. BK2011484 and No. 2012704; National Natural Science Foundation of China, No. 81070287.
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: Sheng-Chun Dang, MD, Department of General Surgery, the Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang 212001, Jiangsu Province, China. dscgu@163.com
Telephone: +86-511-88820988 Fax: +86-511-88820988
Received: September 6, 2014
Peer-review started: September 7, 2014
First decision: October 14, 2014
Revised: November 2, 2014
Accepted: December 5, 2014
Article in press: December 8, 2014
Published online: March 7, 2015
Processing time: 184 Days and 5 Hours
Abstract

AIM: To investigate the protective effect of clodronate-containing liposomes against severe acute pancreatitis (SAP)-triggered acute gastric mucosal injury (AGMI) in rats.

METHODS: Clodronate- and phosphate-buffered saline (PBS)-containing liposomes were prepared by reverse-phase evaporation. The SAP rat model was established by injecting sodium taurocholate into the pancreatic subcapsular space. Sprague-Dawley rats were randomly divided into three groups: control (C), SAP plus PBS-containing liposome (P) and SAP plus clodronate-containing liposome (T). Serum tumor necrosis factor (TNF)-α levels were estimated by ELISA. Pathological changes in the gastric mucosa and pancreas were observed by hematoxylin and eosin (HE) staining. Apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The numbers of macrophages in the gastric mucosa were analyzed by CD68 immunohistochemical staining.

RESULTS: The liposomes had a mean diameter of 150 ± 30 nm. The TNF-α levels were significantly higher in the P group than that in the C group (2 h, 145.13 ± 11.50 vs 23.2 ± 2.03; 6 h, 245.06 ± 12.11 vs 30.28 ± 6.07, P < 0.05), and they were significantly lower in the T group than that in the P group (2 h, 93.24 ± 23.11 vs 145.13 ± 11.50; 6 h, 135.18 ± 13.10 vs 245.06 ± 12.11, P < 0.05). The pathological scores of the pancreas were lower in the T group than in the P group (2 h, 1.88 ± 0.83 vs 4.13 ± 0.83; 6 h, 2.87 ± 0.64 vs 6.25 ± 0.88, P < 0.01). The pathological scores of the gastric mucosa were also lower in the T group than in the P group (2 h, 1.12 ± 0.64 vs 2 ± 0.75; 6 h, 1.58 ± 0.53 vs 3 ± 1.31, P < 0.05). In addition, increased CD68 levels were observed in the gastric mucosa of the P group compared with the C group. Clodronate-containing liposomes decreased the CD68 levels in the mucosa of the T group. The apoptotic indexes of the gastric mucosa were higher in the T group than in the P group (2 h, 15.7 ± 0.92 vs 11.5 ± 1.64; 6 h, 21.12 ± 1.06 vs 12.6 ± 2.44, P < 0.01).

CONCLUSION: Gastric macrophages contribute to the pathogenesis of gastric injury in SAP. Clodronate-containing liposomes have protective effects against AGMI in rats with SAP.

Keywords: Pancreatitis; Clodronate disodium; Macrophage; Gastric mucosal injury

Core tip: In this study, we investigated the protective effect of clodronate liposomes against severe acute pancreatitis (SAP)-triggered acute gastric mucosal injury in rats. Our results revealed that gastric macrophages are involved in the pathogenesis of gastric injury in SAP. Moreover, clodronate-containing liposomes have protective effects against gastric mucosal injury in rats with SAP. Therefore, the blockade of macrophage infiltration may represent a novel therapeutic strategy for the treatment of SAP.