Abstract

It has been demonstrated that vagus nerve stimulation (VNS) plays a protective role in ischemia/reperfusion (I/R) injury of various organs. The present study investigates the protective effect of VNS on hepatic I/R injury and the potential mechanisms. Male Sprague-Dawley rats were randomly allocated into three groups: the sham operation group (Sham; n = 6, sham surgery with sham VNS); the I/R group (n = 6, hepatic I/R surgery with sham VNS); and the VNS group (n = 6, hepatic I/R surgery plus VNS). The I/R model was established by 1 hour of 70% hepatic ischemia. Tissue samples and blood samples were collected after 6 hours of reperfusion. The left cervical vagus nerve was separated and stimulated throughout the whole I/R process. The stimulus intensity was standardized to the voltage level that slowed the sinus rate by 10%. VNS significantly reduced the necrotic area and cell death in I/R tissues. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were also decreased by VNS. In addition, VNS suppressed inflammation, oxidative stress, and apoptosis in I/R tissues. VNS significantly increased the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) in the liver. These data indicated that VNS may attenuate hepatic I/R injury by inhibiting inflammation, oxidative stress, and apoptosis possibly via the Nrf2/HO-1 pathway.

Highlights

  • Hepatic ischemia/reperfusion (I/R) damage often occurs during liver surgery procedures, such as liver resection and liver transplantation [1]

  • These findings indicated that vagus nerve stimulation (VNS) improved hepatic I/R injury

  • These results indicated that the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway induced in the I/R liver was enhanced by VNS

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Summary

Introduction

Hepatic ischemia/reperfusion (I/R) damage often occurs during liver surgery procedures, such as liver resection and liver transplantation [1]. A number of studies have demonstrated that vagus nerve stimulation (VNS) plays a protective role in I/R injury of the kidney, heart, and other organs [8,9,10]. Α7nAChR activation has been shown to enhance the Nrf2/HO-1 pathway [12,13,14,15]. It is still unclear whether VNS can protect against hepatic I/R injury. An acute model of hepatic I/R injury in rats was used to evaluate the protective effect of VNS, and the potential mechanisms were explored

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