Vagus nerve stimulation attenuates acute kidney injury induced by hepatic ischemia/reperfusion injury 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 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 I/R 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 regulated the expression levels of various iconic factors 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 suggested 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.

The protective role of vagus nerve stimulation in ischemia-reperfusion injury

“…Furthermore, proteomic analysis revealed that plasma glutathione and glutathione peroxidase levels were significantly increased by VNS, implying that the protective effect may be related to glutathione metabolism. Furthermore, VNS can also protect distal organs against hepatic IR-induced injury, such as the lung, kidney and skeletal muscle [ [155] , [156] , [157] ]. Currently, there are no clinical trials examining the effect of VNS on hepatic IRI patients, and further studies are needed to confirm its effectiveness.…”

The protective effect of vagus nerve stimulation against myocardial ischemia/reperfusion injury: pooled review from preclinical studies

“…Subsequent research has increasingly suggested that VNS can also confer protection against heart failure progression, due to the restoration of autonomic balance, baroreceptor sensitivity, and electrical stability ( Capilupi et al, 2020 ; Verrier et al, 2022 ; Elamin et al, 2023 ). Recent studies have progressively unveiled the role of VNS in mitigating myocardial I/R injury through the activation of the cholinergic anti-inflammatory pathway, anti-oxidative stress response, or anti-apoptotic response ( Chen et al, 2020 ; Wang et al, 2020 ; Deng et al, 2022 ). However, the intricate mechanisms underlying VNS-mediated cardioprotection in experimental studies, along with limited clinical evidence, pose obstacles to its broader application in clinical practice.…”