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Vagus nerve stimulation (VNS) may participate in maintaining oxidative homeostasis and response to external stimulus or injury. We investigated whether the <jats:italic>in vivo<\/jats:italic> VNS can protect the liver from IRI. In this study, hepatic IRI were induced by ligating the vessels supplying the left and middle lobes of the liver, which underwent 1\u2009h occlusion followed with 24\u2009h reperfusion. VNS was initiated 15\u2009min after ischemia and continued 30\u2009min. Hepatic function, histology, and apoptosis rates were evaluated after 24\u2009h reperfusion. Compared with the IRI group, VNS significantly improved hepatic function. The protective effect was accompanied by a reduction in histological damage in the ischemic area, and the apoptosis rate of hepatocytes has considerable reduction. To find the underlying mechanism, proteomic analysis was performed and differential expression of glutathione synthetase (GSS) and glutathione S-transferase (GST) was observed. Subsequently, test results indicated that VNS upregulated the expression of mRNA and protein of GSS and GST. Meanwhile, VNS increased the plasma levels of glutathione and glutathione peroxidases. We found that VNS alleviated hepatic IRI by upregulating the antioxidant glutathione via the GSS\/glutathione\/GST signaling pathway.<\/jats:p>","DOI":"10.1155\/2020\/1079129","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T18:30:49Z","timestamp":1579717849000},"page":"1-15","source":"Crossref","is-referenced-by-count":14,"title":["Vagus Nerve Stimulation Alleviates Hepatic Ischemia and Reperfusion Injury by Regulating Glutathione Production and Transformation"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8630-0738","authenticated-orcid":true,"given":"Haoyang","family":"Xia","sequence":"first","affiliation":[{"name":"Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Engineering Research Center of Natural Polymer-Based Medical Materials in Hubei Province, Wuhan 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