Xiaozhang Tie Improves Intestinal Motility in Rats With Cirrhotic Ascites by Regulating the Stem Cell Factor/c-kit Pathway in Interstitial Cells of Cajal.

Qiang Zhao,Feng Xing,Nianping Feng,Yuan Peng,Hongliang Liu,Chenghai Liu,Yanyan Tao,Kai Huang

doi:10.3389/fphar.2020.00001

Abstract

We previously discovered that Xiaozhang Tie (XZT) was helpful for cirrhotic ascites, with obvious abdominal distention relief, suggesting that it may improve gastrointestinal (GI) motility. However, the underlying mechanisms of GI motility in cirrhotic ascites are unclear. Here, we aimed to discover explored the effect of XZT on GI motility in animal cirrhotic ascites and probed the action mechanism affecting GI motility by regulating the stem cell factor (SCF)/c-kit pathway in interstitial cells of Cajal (ICCs) and GI hormones. First, rat models of cirrhotic ascites were developed and then divided randomly into the following three subgroups: model control, XZT group, and mosapride group. The efficacy of XZT on treating cirrhotic ascites was evaluated on the basis of ascites weight and volume, 24 h urine volume, and feces water content. GI motility of the cirrhotic model, intestine propulsion, and gastric residue were detected using the migration distance of ink in vivo, and the frequency of contraction and tension of isolated gastric and jejunal muscle strips were measured after incubation with XZT extracts. Serum GI hormone content, including motilin (MTL), substance P (SP), somatostatin (SS), and vasoactive intestinal polypeptide were assayed. Subsequently, ICCs were isolated from jejunum, and primarily cultured ICCs were incubated with and without XZT and SCF. The cell vitality of the ICCs was measured. A whole-cell patch recording technique was used to record the current of K+ and Na+ channels in the ICC membrane. Expressions of c-kit/p-c-kit, p-Akt, p-STAT3, and p-Erk1/2 were detected in vivo and in vitro. The results revealed that XZT significantly reduced ascites weight and increased urine volume and fecal water content in model rats. XZT promoted intestinal motility and increased MTL level but reduced SP and SS levels. It enhanced the current of Na+ and K+ in ICCs and improved c-kit expression and signaling mediator phosphorylation in SCF/c-kit, which was inhibited by imatinib in vitro and downregulated in model rats in vivo. Our study concluded that XZT reduced the amount of ascites and improved intestinal motility in cirrhotic rats, which may be associated with its effect on ascites and was involved in the mechanisms regulating the SCF/c-kit signaling pathway in ICCs and improving gastrointestinal hormone secretion.

Highlights

Ascites is the most common clinical manifestation of cirrhosis (Runyon and Committee, 2009) and is an indicator that cirrhosis has developed from the compensation stage to the decompensation stage
High ascites/weight ratio accompanied by reduced 24 h urine volume and fecal water content were observed in the cirrhotic rats, and all pathological phenomena were effectively reversed by XZT but not by mosapride (Figures 1A–E)
Gastric and jejunal muscle strips isolated from two normal and four cirrhotic ascites rats were incubated with XZT extract at different concentrations to screen for the optimal concentration

Summary

Introduction

Ascites is the most common clinical manifestation of cirrhosis (Runyon and Committee, 2009) and is an indicator that cirrhosis has developed from the compensation stage to the decompensation stage. It affects the quality of life of patients but is closely related to other complications of cirrhosis, such as endotoxemia, spontaneous bacterial peritonitis, hepatorenal syndrome, and gastrointestinal dysfunction. One is drug therapy, including diuretics and human serum albumin. Another is invasive therapy, such as peritoneal paracentesis and autoinfusion of concentrated ascites. A suitable method for the management of cirrhotic ascites, refractory ascites in particular, remains to be identified, and new treatments are required

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