scholarly journals Vagus Nerve Stimulation Attenuates Hepatic Ischemia/Reperfusion Injury via the Nrf2/HO-1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Qianqian Zhang ◽  
Yanqiu Lai ◽  
Jielin Deng ◽  
Menglong Wang ◽  
Zhenya Wang ◽  
...  

It has been demonstrated that vagus nerve stimulation (VNS) plays a protective role in ischemia/reperfusion (I/R) injury of various organs. The present study investigates the protective effect of VNS on hepatic I/R injury and the potential mechanisms. Male Sprague-Dawley rats were randomly allocated into three groups: the sham operation group (Sham; n=6, sham surgery with sham VNS); the I/R group (n=6, hepatic I/R surgery with sham VNS); and the VNS group (n=6, hepatic I/R surgery plus VNS). The I/R model was established by 1 hour of 70% hepatic ischemia. Tissue samples and blood samples were collected after 6 hours of reperfusion. The left cervical vagus nerve was separated and stimulated throughout the whole I/R process. The stimulus intensity was standardized to the voltage level that slowed the sinus rate by 10%. VNS significantly reduced the necrotic area and cell death in I/R tissues. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were also decreased by VNS. In addition, VNS suppressed inflammation, oxidative stress, and apoptosis in I/R tissues. VNS significantly increased the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) in the liver. These data indicated that VNS may attenuate hepatic I/R injury by inhibiting inflammation, oxidative stress, and apoptosis possibly via the Nrf2/HO-1 pathway.

2022 ◽  
Vol 12 ◽  
Author(s):  
Ying Xin ◽  
Yifeng Zhang ◽  
Simin Deng ◽  
Xinqun Hu

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.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yifeng Zhang ◽  
Hewei Li ◽  
Menglong Wang ◽  
Guannan Meng ◽  
Zhenya Wang ◽  
...  

Vagus nerve stimulation (VNS) has been shown to attenuate ischemia-reperfusion (I/R) injury in multiple organs. The present study aimed at investigating whether VNS could exert protective effects against I/R injury in the skeletal muscle. Male Sprague-Dawley rats were randomly divided into 3 groups: the control, I/R, and I/R+VNS groups. The skeletal muscle I/R (SMI/R) model was induced by occlusion of the left femoral artery for 2.5 hours followed by reperfusion for 2 hours. The vagal nerve trunk was separated, and VNS was performed during the whole I/R process. The intensity of VNS was optimized in each rat to obtain a 10% reduction in the heart rate relative to the value before stimulation. After the experiment, the blood sample and left gastrocnemius muscle tissues were collected for histological examination, biochemical analysis, and molecular biological detection. During the I/R process, VNS significantly reduced cellular apoptosis, necrosis, and inflammatory cell infiltration compared to sham VNS. The VNS treatment also decreased the inflammatory response, alleviated oxidative stress, and improved vascular endothelial function (p<0.05 for each). In contrast, the I/R group showed an opposite effect compared to the control group. The present study indicated that VNS could protect against SMI/R injury by suppressing excessive inflammation, alleviating oxidative stress, and preserving vascular endothelial function.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Haoyang Xia ◽  
Zhongzhong Liu ◽  
Wenjin Liang ◽  
Xianpeng Zeng ◽  
Yi Yang ◽  
...  

Inflammation and oxidative stress are pivotal mechanisms for the pathogenesis of ischemia and reperfusion injury (IRI). Vagus nerve stimulation (VNS) may participate in maintaining oxidative homeostasis and response to external stimulus or injury. We investigated whether the in vivo 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 h occlusion followed with 24 h reperfusion. VNS was initiated 15 min after ischemia and continued 30 min. Hepatic function, histology, and apoptosis rates were evaluated after 24 h 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.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Meng Wang ◽  
Jielin Deng ◽  
Huanzhu Lai ◽  
Yanqiu Lai ◽  
Guannan Meng ◽  
...  

Objective. In renal ischemia/reperfusion injury (RIRI), nuclear factor κB (NF-κB) initiates the expression of multiple genes involved in inflammatory disease. Inhibition of NF-κB-mediated inducible nitric oxide synthase (iNOS) expression can ameliorate RIRI. Vagus nerve stimulation (VNS) protects against various organs I/R injury. The present study was designed to elucidate the protective effect of VNS on RIRI and its influence on iNOS protein expression. Methods. Eighteen male Sprague-Dawley rats were randomly allocated into the sham group, the I/R group, and the VNS+I/R group, 6 rats per group. An RIRI model was induced by a right nephrectomy and blockade of the left renal pedicle vessels for 45 min. After 6 h of reperfusion, the blood samples and renal samples were collected. The VNS treatment was performed throughout the I/R process in the VNS+I/R group using specific parameters (20 Hz, 0.1 ms in duration, square waves) known to produce a small but reliable bradycardia. Blood was used for evaluation of renal function and inflammatory state. Renal injury was evaluated via TUNEL staining. Renal samples were harvested to evaluate renal oxidative stress, NF-κB p65 levels, and iNOS protein expression. Results. The VNS treatment reduces serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Simultaneously, the levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1-beta (IL-1β) were significantly increased in the I/R group, but VNS treatment markedly ameliorated this inflammatory response. Furthermore, the VNS ameliorated oxidant stress and renal injury, indicated by a decrease in 3-nitrotyrosine (3-NT) formation and MDA and MPO levels and an increase in the SOD level compared to that in the I/R group. Finally, the VNS also significantly decreases NF-κB p65, iNOS, and nitrite/nitrate levels compared to that in the I/R group. Conclusion. Our findings indicate that NF-κB activation increased iNOS expression and promoted RIRI and that VNS treatment attenuated RIRI by inhibiting iNOS expression, oxidative stress, and inflammation via NF-κB inactivation.


Sign in / Sign up

Export Citation Format

Share Document