Abstract
Liver ischemia-reperfusion injury (IRI) is an inevitable process during liver transplantation, hemorrhagic shock, resection, and other liver surgeries. It is an important cause of postoperative liver dysfunction and increased medical costs. The protective effects of the vagus nerve on hepatic IRI have been reported, but the underlying mechanism has not been fully understood. We established a hepatic vagotomy (Hv) mouse model to study the effect of the vagus on liver IRI and to explore the underlying mechanism. Liver IRI was more serious in mice with Hv, which showed higher serum ALT and AST activities and histopathological changes. Further experiments confirmed that Hv significantly downregulated the expression of IL-22 protein and mRNA in the liver, blocking the activation of the STAT3 pathway. The STAT3 pathway in the livers of Hv mice was significantly activated, and liver injury was clearly alleviated after treatment with exogenous IL-22 recombinant protein. In conclusion, Hv can aggravate hepatic IRI, and its mechanism may be related to inhibition of IL-22 expression and downregulation of the STAT3 pathway in the liver.
Highlights
Hepatic ischemia-reperfusion injury (IRI) is an inevitable process during liver transplantation, hemorrhagic shock, resection, and other liver surgeries [1,2,3,4]
Compared with the IRI-Sham group, mice in the IRI-hepatic vagotomy (Hv) group showed larger infarct sizes and more complete hepatocyte necrosis at different observation time points, indicating that the hepatic branch of the vagus has a protective effect on liver injury induced by ischemia-reperfusion
The expression of IL-22 protein was hardly seen at any time point in the IRI-Hv group (Figure 3(f)). These results suggest that Hv can inhibit the production of IL-22 induced by IRI
Summary
Hepatic ischemia-reperfusion injury (IRI) is an inevitable process during liver transplantation, hemorrhagic shock, resection, and other liver surgeries [1,2,3,4]. Zhang et al [12] found that when the left cervical vagal trunk (the origin of the hepatic vagus nerve) was stimulated with a high-frequency electrode, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) was markedly increased, Journal of Immunology Research which alleviated liver IRI by inhibiting oxidative stress, inflammation, and apoptosis in the liver Another group established a hepatic vagotomy mouse model and showed that the vagus nerve could reduce IR-induced hepatocyte apoptosis by activating α7 nicotinic acetylcholine receptor (α7nAChR) on Kupffer cells (KCs) to prevent excessive reactive oxygen species production in KCs [13]. The effect of the vagus on hepatocytes involves a variety of cytokines, chemokines, and signaling pathways, which we still know little about
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