Abstract

Purpose: This article aimed to study the role of sevoflurane pre-conditioning in hepatic ischemia–reperfusion and its potential mechanism.Methods: Rat liver ischemia–reperfusion model was constructed. Serum TNF-α, IL-1β, IL-10, and IL-6 concentrations were detected by ELISA. Malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) in liver homogenate were determined. Hematoxylin–Eosin (HE) staining, Tunel, and immunohistochemistry were performed. Ischemia–reperfusion hepatocyte model was established. Cells transfection was conducted. Apoptosis was observed by flow cytometry. Quantitative real-time PCR (qRT-PCR) and Western blotting analysis were used.Results: Compared with I/R group, liver damage degree, liver cell apoptosis, and glucose regulatory protein 78 (Grp78) expression was obviously reduced in rats of SEV group. TNF-α, IL-1β, and IL-6 concentrations were also significantly increased (P<0.01). MDA and NO concentrations were dramatically lower (P<0.01) and SOD concentration was significantly higher (P<0.01). Apoptosis rate, Grp78, PERK, eIF2α, and p-c-JNK/JNK expression was also significantly decreased (P<0.01). Sevoflurane significantly reduced apoptosis and expression of PERK, eIF2α, p-c-JNK/JNK by inhibiting the expression of Grp78 (P<0.01).Conclusion: Sevoflurane relieves hepatic ischemia–reperfusion injury by inhibiting the expression of Grp78.

Highlights

  • Ischemic reperfusion is a necessary part of liver surgery or liver transplantation

  • We explored the effects of sevoflurane pre-conditioning on hepatic ischemia–reperfusion injury in rats, and further investigated its effect on ischemia–reperfusion hepatocytes in vitro by using BNL CL.2 cells

  • Further in vitro studies revealed that sevoflurane pre-conditioning could reduce hepatocyte apoptosis and PERK, eIF2α, and p-c-JNK expression by inhibiting glucose regulatory protein 78 (Grp78) expression

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Summary

Introduction

Ischemic reperfusion is a necessary part of liver surgery or liver transplantation. Inevitable hepatocellular damage can be caused during ischemia process and liver function is unlikely to quickly return to normal after reperfusion [1]. Liver inflammation, damage, and even severe liver dysfunction would be occurred after surgery [2]. Severe liver ischemia–reperfusion injury can lead to multiple organ failure and even death, which is one of the key factors that cause severe adverse prognosis [3]. Prevention and alleviation of hepatic ischemia–reperfusion injury have an important impact on improving patients’ prognosis and reducing their mortality. Discovery of the exact mechanism leading to hepatic ischemia–reperfusion injury was important to improve patients’ prognosis

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