Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Jun 27, 2023; 15(6): 1068-1079
Published online Jun 27, 2023. doi: 10.4240/wjgs.v15.i6.1068
Impact of interstitial cells of Cajal on slow wave and gallbladder contractility in a guinea pig model of acute cholecystitis
Fan Ding, Run Guo, Fang Chen, Li-Ping Liu, Zheng-Yu Cui, Yi-Xing Wang, Gang Zhao, Hai Hu
Fan Ding, Gang Zhao, Hai Hu, Center of Gallbladder Disease, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
Fan Ding, Gang Zhao, Hai Hu, Institute of Gallstone Disease, School of Medicine, Tongji University, Shanghai 200331, China
Run Guo, Fang Chen, Li-Ping Liu, Department of Ultrasonography, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
Zheng-Yu Cui, Yi-Xing Wang, Department of Internal Medicine of Traditional Chinese Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
Author contributions: Ding F and Guo R performed experiments; Hu H, Zhao G, and Wang YX designed the study; Cui ZY performed data analysis; Chen F and Liu LP drafted the manuscript; all authors reviewed the final manuscript.
Supported by the Pudong New Area Clinical Traditional Chinese Medicine of Top Discipline Project, No. PDZY-2018-0603 and the Featured Clinical Discipline Project of Shanghai Pudong, No. PWYts2021-06.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the East Hospital of Tongji University (approval No. 2020-12-102).
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hai Hu, MD, PhD, Director, Center of Gallbladder Disease, Shanghai East Hospital, School of Medicine, Tongji University, No. 150 Jimo Road, Shanghai 200120, China. huhailc@sina.com
Received: December 29, 2022
Peer-review started: December 29, 2022
First decision: February 20, 2023
Revised: February 21, 2023
Accepted: April 14, 2023
Article in press: April 14, 2023
Published online: June 27, 2023
Processing time: 168 Days and 0.9 Hours
Abstract
BACKGROUND

Impaired interstitial cells of Cajal (ICCs) are central to the pathophysiology of acute cholecystitis (AC). Common bile duct ligation is a common model of AC, producing acute inflammatory changes and decrease in gallbladder contractility.

AIM

To investigate the origin of slow wave (SW) in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC.

METHODS

Methylene blue (MB) with light was used to establish selective impaired ICCs gallbladder tissue. Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control (NC), AC12h, AC24h, and AC48h groups of guinea pigs. Hematoxylin and eosin and Masson-stained gallbladder tissues were scored for inflammatory changes. ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy. The alterations of c-Kit, α-SMA, cholecystokinin A receptor (CCKAR), and connexin 43 (CX43) were assessed using Western blot.

RESULTS

Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility. The frequency of SW and gallbladder contractility were significantly lower in the AC12h group. Compared with the NC group, the density and ultrastructure of ICCs were remarkably impaired in the AC groups, especially in the AC12h group. The protein expression levels of c-Kit were significantly decreased in the AC12h group, while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group.

CONCLUSION

Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility. The density and ultrastructure of ICCs were clearly impaired in the early stage of AC, while CCKAR and CX43 were significantly reduced at end stage.

Keywords: Interstitial cells of Cajal, Acute cholecystitis, Slow wave, Gallbladder, Contractility

Core Tip: Acute cholecystitis (AC) is inflammation of the gallbladder. In this study, we found that loss interstitial cells of Cajal (ICCs) could lead to the decreased of gallbladder slow wave (SW) and contractility. Acute inflammation can cause a reduction in the SW and gallbladder motility deficiency by damaging the density and function of ICCs during early AC stage. At the end stage of AC, the decrease of cholecystokinin A receptor and gap junction leads to the further decrease in gallbladder contractility and electrical conductivity.