Published online Jun 27, 2023. doi: 10.4240/wjgs.v15.i6.1068
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
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.
To investigate the origin of slow wave (SW) in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC.
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.
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.
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.
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.