Physical Exercise Repairs Obstructive Jaundice-Induced Damage to Intestinal Mucosal Barrier Function via H2S-Mediated Regulation of the HMGB1/Toll Like Receptors 4/Nuclear Factor Kappa B Pathway.

Changfeng Shao,Rui Chen,Ye Li,Qi Peng,Afang Yuan,Lan Zheng,Jiaqin Chen,Wei Chen

doi:10.3389/fphys.2021.732780

Abstract

The present study aimed to determine the effect of aerobic exercise on improving damage to intestinal mucosal barrier function caused by obstructive jaundice (OJ) and explore the mechanism. Fifty male KM mice were divided into five groups: sham operation group (S), model group (M), exercise group (TM), DL-propargylglycine + exercise (PT) group, and sodium hydrosulfide + exercise (NT) group. Additionally, mice in S group underwent common bile duct ligation for 48 h to establish a murine obstructive jaundice model. In PT group, propargylglycine (40 mg/kg) was intraperitoneally injected 7 days after surgery. NaHS (50 μmol/kg) was intraperitoneally injected into mice in the NT group 7 days after surgery. The TM group, NT group and PT group exercised on a slope of 0% at a speed of 10 m/min without weight training (30 min/day). HE staining showed that the intestinal mucosa of group M was atrophied and that the villi were broken. The intestinal mucosal structure of mice in the TM group was improved. Serum assays showed that H2S levels were higher in the TM group than in the M group; compared with the levels in the TM group, the PT group levels were decreased and the NT group levels were increased. In addition, aerobic exercise inhibits the HMGB1/TLR4/NF-κB signaling pathway by promoting endogenous H2S production, thereby exerting a protective effect on the intestinal mucosal barrier.

Highlights

Obstructive jaundice (OJ) is a life-threatening disease that is common in hepatobiliary tissue (Ishizawa et al, 2007; Jin et al, 2019)
Previous studies have shown that regular aerobic exercise can improve obstructive jaundice (OJ)-induced liver injury, inhibit hepatocyte apoptosis induced by jaundice, and promote hepatocyte proliferation by regulating the expression of factors related to hepatocyte regeneration and delaying liver tissue fibrosis (Haczeyni et al, 2015)
Morphological analysis of the intestinal mucosa in this study showed that the ileum of mice in the OJ group showed severe pathological damage, and intestinal mucosal injury was significantly reduced in mice that underwent exercise training, indicating that 6 weeks of aerobic exercise exerted a significant protective effect on the intestinal mucosal barrier after OJ

Summary

Introduction

Obstructive jaundice (OJ) is a life-threatening disease that is common in hepatobiliary tissue (Ishizawa et al, 2007; Jin et al, 2019). Malignant tumors or stones can block the bile duct, leading to unsuccessful discharge of bile into the intestine (Dimas et al, 2019). In this situation, bile accumulates in the liver, and there is a reduction in bile in the intestine. The accumulation of Physical Exercise and Obstructive Jaundice bile induces biochemical, histological, and immunological changes that result in hepatic injury and even liver failure (Maeda et al, 2019). A lack of bile in the intestine injures the intestinal mucosal barrier, immunological barrier, and biochemical barrier (Banerjee et al, 2016). BT is responsible for releasing inflammatory cytokines and stimulating immune cells, which contributes to systemic inflammation and even multiple organ dysfunction (Zhuang et al, 2019)

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Conclusion