Vagus Nerve Stimulation Attenuates Acute Kidney Injury Induced by Hepatic Ischemia/Reperfusion Injury by Suppressing Inflammation, Oxidative Stress, and Apoptosis in Rats

Abstract Hepatic ischemia reperfusion (I/R) injury, caused by limited blood supply and subsequent blood supply, is a causative factor resulting in morbidity and mortality during liver transplantation (LT) and liver resection. Hepatic I/R injury frequently contributes to remote organ injury, such as kidney, lung, and heart. It has been demonstrated that vagus nerve stimulation (VNS) is effective in remote organ injury after ischemia reperfusion injury. Here, our aim is to investigate the potential action of VNS on hepatic I/R injury-induced acute kidney injury (AKI) and explore its underlying mechanisms. To test this hypothesis, male Sprague-Dawley rats were randomly assigned into three experimental 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). VNS was performed during the entire hepatic I/R process. Our results showed that throughout the hepatic I/R process, VNS significantly reduced inflammation, oxidative stress, and apoptosis, and greatly enhanced the protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) in the kidneys. These findings suggest that VNS may ameliorate hepatic I/R injury-induced AKI by suppressing inflammation, oxidative stress, and apoptosis probably through activating the Nrf2/HO-1 signaling pathway.