Abstract

This study investigated the protective effect and mechanism of electroacupuncture at ST36 points on the intestinal barrier dysfunction and remote organ injury after intestinal ischemia and reperfusion injury in rats. Rats were subjected to gut ischemia for 30 min, and then received electroacupuncture for 30 min with or without abdominal vagotomy or intraperitoneal administration of cholinergic α7 nicotinic acetylcholine receptor (α7nAChR) inhibitor. Then we compared its effects with electroacupuncture at nonchannel points, vagal nerve stimulation, or intraperitoneal administration of cholinergic agonist. Cytokine levels in plasma and tissue of intestine, lung, and liver were assessed 60 min after reperfusion. Intestinal barrier injury was detected by histology, gut injury score, the permeability to 4 kDa FITC-dextran, and changes in tight junction protein ZO-1 using immunofluorescence and Western blot. Electroacupuncture significantly lowered the levels of tumor necrosis factor-α and interleukin-8 in plasma and organ tissues, decreased intestinal permeability to FITC-dextran, and prevented changes in ZO-1 protein expression and localization. However, abdominal vagotomy or intraperitoneal administration of cholinergic α7nAChR inhibitor reversed these effects of electroacupuncture. These findings suggest that electroacupuncture attenuates the systemic inflammatory response through protection of intestinal barrier integrity after intestinal ischemia injury in the presence of an intact vagus nerve.

Highlights

  • Intestine ischemia and reperfusion injury are usually secondary to a variety of diseases, such as multiple trauma, severe burn, various forms of shock, intra-abdominal sepsis, surgical operation, and inflammatory bowel disease

  • The difficulty in translating these findings to clinical implications is that direct electrical stimulation of the vagus nerve is impractical in acutely injured patients for its complicated operation and adverse effects

  • The actions of electroacupuncture (EA) at ST36 acupoints in rats demonstrated protective effects on reducing local gut inflammation and intestinal barrier breakdown through activating the cholinergic anti-inflammatory-dependent mechanism and involved α7 nicotinic acetylcholine receptor (α7nAChR). This is the first time that ZO1 has been used in evaluating the effect of electroacupuncture group (EA) in preventing intestinal barrier breakdown

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Summary

Introduction

Intestine ischemia and reperfusion (iI/R) injury are usually secondary to a variety of diseases, such as multiple trauma, severe burn, various forms of shock, intra-abdominal sepsis, surgical operation, and inflammatory bowel disease. Bacteria and its endotoxin shift to circulation and remote organs such as lung and liver, contributing to the subsequent local and systemic inflammation, which may lead to systemic inflammation response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and possibly, death [1, 2]. This evidence suggest that the loss of epithelial cell integrity and barrier function of intestine may very well be a source or promoter for the systemic inflammatory process and MODS. It is still difficult to apply electrical stimulation to the vagus nerve in clinical practice due to complicated manipulation and untoward side effects, including serious tissue injury

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