Basic Study
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World J Gastroenterol. Feb 7, 2015; 21(5): 1518-1530
Published online Feb 7, 2015. doi: 10.3748/wjg.v21.i5.1518
CNP signal pathway up-regulated in rectum of depressed rats and the interventional effect of Xiaoyaosan
Ping Li, Xu-Dong Tang, Zheng-Xu Cai, Juan-Juan Qiu, Xue-Lian Lin, Tong Zhu, Lawrence Owusu, Hui-Shu Guo
Ping Li, Zheng-Xu Cai, Juan-Juan Qiu, Xue-Lian Lin, Tong Zhu, Lawrence Owusu, Hui-Shu Guo, Central Laboratory, Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
Xu-Dong Tang, Department of Gastroenterology, Xi yuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
Author contributions: Li P and Tang XD contributed equally to this work, they are co-first authors; Li P, Tang XD, Cai ZX and Guo HS designed the research; Li P, Qiu JJ, Lin XL and Zhu T performed the research; Li P and Lin XL analyzed the data; Li P and Guo HS wrote the paper; Owusu L and Guo HS revised the paper.
Supported by National Natural Science Foundation of China, No. 81273919; Grants from the Natural Science Foundation of Liaoning Province, No. 2012225020 and No. 2013023002; and the National Basic Research Program of China (973 Program), No. 2013CB531703.
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: Hui-Shu Guo, Professor, Central Laboratory, Department of Neurology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian 116011, Liaoning Province, China. guohuishu1@126.com
Telephone: +86-0411-83635963 Fax: +86-411-8362-2844
Received: July 27, 2014
Peer-review started: July 28, 2014
First decision: August 6, 2014
Revised: August 28, 2014
Accepted: October 21, 2014
Article in press: October 21, 2014
Published online: February 7, 2015
Processing time: 197 Days and 3 Hours
Abstract

AIM: To investigate the distribution and expression of C-type natriuretic peptide (CNP)/natriuretic peptide receptor B (NPR-B) in the rectum of a rodent depression model and the interventional effect of Xiaoyaosan (XYS).

METHODS: Male rats (n = 45) of clean grade (200 ± 20 g) were divided into five groups after one week of adaptive feeding: primary control, depression model, low dose XYS, middle dose XYS, and high dose XYS. The animal experiment continued for 3 wk. Primary controls were fed normally ad libitum. The rats of all other groups were raised in solitary and exposed to classic chronic mild unpredictable stimulation each day. XYS groups were perfused intragastrically with low dose, middle dose, and high dose XYS one hour before stimulation. Primary control and depression model groups were perfused intragastrically with normal saline under similar conditions as the XYS groups. Three weeks later, all rats were sacrificed, and the expression levels of CNP and NPR-B in rectum tissues were analyzed by immunohistochemistry, real-time polymerase chain reaction, and Western blotting.

RESULTS: CNP and NPR-B were both expressed in the rectum tissues of all rats. However, the expression levels of CNP and NPR-B at both gene and protein levels in the depression model group were significantly higher when compared to the primary control group (n = 9; P < 0.01). XYS intervention markedly inhibited the expression levels of CNP and NPR-B in depressed rats. The expression levels of CNP and NPR-B in the high dose XYS group did not significantly differ from the expression levels in the primary control group. Additionally, the high and middle dose XYS groups (but not the low dose group) significantly exhibited lower CNP and NPR-B expression levels in the rectum tissues of the respectively treated rats compared to the untreated depression model cohort (n = 9; P < 0.01).

CONCLUSION: The CNP/NPR-B pathway is upregulated in the rectum of depressed rats and may be one mechanism for depression-associated digestive disorders. XYS antagonizes this pathway at least partially.

Keywords: C-Type natriuretic peptide; Natriuretic peptide receptor type B; Rectum; Depression; Gastrointestinal motility

Core tip: C-type natriuretic peptide (CNP) and natriuretic peptide receptor B (NPR-B) were expressed in the mucosa, muscle, and serosa of rat rectum. Expression of CNP and NPR-B are upregulated in the rectum of depressive digestive disorder rats, with the CNP/NPR-B signal pathway possibly being involved in depressive digestive disorders. Our study shows that Xiaoyaosan inhibits the expression of CNP and NPR-B in a dose-dependent manner.