Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2016; 22(24): 5540-5547
Published online Jun 28, 2016. doi: 10.3748/wjg.v22.i24.5540
Effects of sphincter of Oddi motility on the formation of cholesterol gallstones
Zhong-Hou Rong, Hong-Yuan Chen, Xin-Xing Wang, Zhi-Yi Wang, Guo-Zhe Xian, Bang-Zhen Ma, Cheng-Kun Qin, Zhen-Hai Zhang
Zhong-Hou Rong, Hong-Yuan Chen, Xin-Xing Wang, Zhi-Yi Wang, Guo-Zhe Xian, Bang-Zhen Ma, Cheng-Kun Qin, Zhen-Hai Zhang, Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shangdong University, Jinan 250021, Shandong Province, China
Author contributions: Rong ZH and Zhang ZH contributed equally to this work; Zhang ZH, Rong ZH, Xian GZ, and Qin CK designed the research; Rong ZH, Chen HY, Wang XX, Wang ZY, and Ma BZ performed the research; Rong ZH and Zhang ZH analyzed the data; Rong ZH and Zhang ZH wrote the paper.
Supported by Natural Science Foundation of Shandong Province, China, No. ZR 2012 HM -079.
Institutional review board statement: The study was reviewed and approved by the Provincial Hospital Affiliated to Shangdong University Institutional Review Board.
Institutional animal care and use committee statement: The animal protocol was designed to minimize pain or discomfort to the animals. The animals were acclimatized to laboratory conditions (room temperature 23 °C, 12-h light and dark cycle, 50% humidity, ad libitum access to food and water) for two weeks prior to experimentation. All animals were euthanized by barbiturate overdose (intravenous injection, 150 mg/kg pentobarbital sodium) for tissue collection.
Conflict-of-interest statement: The authors declare there is no conflict of interest related to this study.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at zhangzhenhai410@126.com. Participants gave informed consent for data sharing.
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: Zhen-Hai Zhang, PhD, Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shangdong University, No. 324 Jingwuweiqi Road, Jinan 250021, Shandong Province, China. zhangzhenhai410@126.com
Telephone: +86-531-68776363 Fax: +86-531-68776363
Received: January 31, 2016
Peer-review started: February 1, 2016
First decision: March 7, 2016
Revised: March 30, 2016
Accepted: April 20, 2016
Article in press: April 20, 2016
Published online: June 28, 2016
Processing time: 141 Days and 23.7 Hours
Abstract

AIM: To investigate the mechanisms and effects of sphincter of Oddi (SO) motility on cholesterol gallbladder stone formation in guinea pigs.

METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group (n = 10) and the cholesterol gallstone group (n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor (CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR (qRT-PCR) and serum vasoactive intestinal peptide (VIP), gastrin, and cholecystokinin octapeptide (CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation.

RESULTS: The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups.

CONCLUSION: A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.

Keywords: Cholesterol gallstone; Sphincter of Oddi; Manometry; Myoelectric activity; Cholecystokinin-A receptor

Core tip: This study investigated the role of sphincter of Oddi (SO) motility in cholesterol gallstone formation in a guinea pig model. The myoelectric activity and manometry of SO were measured at different stages of stone formation. As SO motility is controlled by neurological and hormonal factors, we detected the expression of serum vasoactive intestinal peptide (VIP), gastrin, cholecystokinin octapeptide (CCK-8), and CCK-A receptor (CCKAR) in the SO at different stages of stone formation. We found that a cholesterol gallstone-causing diet can induce SO dysfunction and expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.