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

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.

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.…”

Putative role of non‐invasive vagus nerve stimulation in cancer pathology and immunotherapy: Can this be a hidden treasure, especially for the elderly?

“…Oxidative stress is a pathological process that results from an imbalance between the production and accumulation of reactive oxygen species such as superoxide radicals, hydrogen peroxide, hydroxyl radicals, and singlet oxygen in the cells and the ability of the body system to detoxify them 76,77 . Vagus nerve stimulation (VNS) reduces oxidative stress via silent information regulator 1 (SIRT1), which is a histone of deacetylase of nicotinamide adenine dinucleotide (NAD + ) that helps in the regulation of cell proliferation, differentiation, apoptosis, and metabolism 71,78 …”

“…In particular, several important mechanisms have been identified: oxidative stress reduction; inhibition of inflammatory response by targeting two inflammation pathways (the hypothalamic-pituitaryadrenal axis (HPA) and the cholinergic anti-inflammatory pathway) and inhibition of sympathetic activity. 48,70,71 See Table 1 for the summary of the potential VNS parameters The stimulation started 24 h prior to the operation and continued till the 4th postoperative day for patients with cancer [72][73][74][75] ; and Figure 1 for the schematic representation of its mechanisms.…”

Vagus nerve stimulation attenuates acute kidney injury induced by hepatic ischemia/reperfusion injury in rats

“…Additionally, VNS has been proven to reduce I/R injury in multiple organs, including the kidneys, brain, and heart [9][10][11] . Furthermore, an increasing number of researchers are becoming aware of the potential of VNS on remote organ injury after I/R injury [12][13][14] . However, to the best of our knowledge, whether VNS can also reduce remote kidney injury after hepatic I/R injury remains unknown.…”

“…Subsequently, continuous low-frequency stimulation (HFS, 20 Hz, 0.2 ms in duration, square waves) were delivered. VNS was performed during the entire hepatic I/R process 12 . The stimulus intensity should achieve a 10% reduction in the sinus rate and adjust hourly 10,37 .…”