Vagus Nerve Stimulation Attenuates Acute Skeletal Muscle Injury Induced by Hepatic Ischemia/Reperfusion Injury in Rats.

Ying Xin,Yifeng Zhang,Simin Deng,Xinqun Hu

doi:10.3389/fphar.2021.756997

Abstract

Vagus nerve stimulation (VNS) has a protective effect on distal organ injury after ischemia/reperfusion (I/R) injury. We aimed to investigate the protective efficacy of VNS on hepatic I/R injury-induced acute skeletal muscle injury and explore its underlying mechanisms. To test this hypothesis, male Sprague-Dawley rats were randomly divided into three groups: sham group (sham operation, n = 6); I/R group (hepatic I/R with sham VNS, n = 6); and VNS group (hepatic I/R with VNS, n = 6). A hepatic I/R injury model was prepared by inducing hepatic ischemia for 1 h (70%) followed by hepatic reperfusion for 6 h. VNS was performed during the entire hepatic I/R process. Tissue and blood samples were collected at the end of the experiment for biochemical assays, molecular biological preparations, and histological examination. Our results showed that throughout the hepatic I/R process, VNS significantly reduced inflammation, oxidative stress, and apoptosis, while significantly increasing the protein levels of silent information regulator 1 (SIRT1) and decreasing the levels of acetylated forkhead box O1 and Ac-p53, in the skeletal muscle. These data suggest that VNS can alleviate hepatic I/R injury-induced acute skeletal muscle injury by suppressing inflammation, oxidative stress, and apoptosis, potentially via the SIRT1 pathway.

Highlights

For Hepatic ischemia/reperfusion (I/R) injury during liver surgery, such as liver transplantation and liver resection, is an important pathophysiological process leading to liver injury, which accelerates the progression of diseases such as acute liver injury and liver failure (Al-Saeedi et al, 2018; Ni et al, 2019)
These results indicate that Vagus nerve stimulation (VNS) may have a protective effect against skeletal muscle injury after hepatic ischemia/ reperfusion (I/R) injury
We found that hepatic I/R injury induced obvious skeletal muscle injury, characterized by muscle fiber disorder, stripe loss, and inflammatory cell infiltration; VNS alleviated this injury

Summary

Introduction

For Hepatic ischemia/reperfusion (I/R) injury during liver surgery, such as liver transplantation and liver resection, is an important pathophysiological process leading to liver injury, which accelerates the progression of diseases such as acute liver injury and liver failure (Al-Saeedi et al, 2018; Ni et al, 2019). Skeletal muscles account for approximately 40% of body weight in lean men and women, making up the largest organ in non-obese people (Guridi et al, 2015). It is an important metabolic organ of the body, which is believed to have the ability to produce hundreds of secretory factors, which can be released into the circulation, directly or indirectly affecting the functions of other organs, establish connections with other tissues and organs, participate in the regulation of oxidative stress, and play a role in anti-I/ R (Pedersen and Febbraio, 2012; Szabó et al, 2020). Skeletal muscle is susceptible to hepatic I/R injury, which leads to acute skeletal muscle injury and accelerates the progression of disease

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