Overexpression of Brg1 Alleviates Hepatic Ischemia/Reperfusion-Induced Acute Lung Injury through Antioxidative Stress Effects.

Weifeng Yao,Shaoli Zhou,Jun Cai,Mian Ge,Chaojin Chen,Ziqing Hei,Fei Huang

doi:10.1155/2017/8787392

Abstract

Aim To investigate whether overexpression of Brahma-related gene-1 (Brg1) can alleviate lung injury induced by hepatic ischemia/reperfusion (HIR) and its precise mechanism. Methods Cytomegalovirus-transgenic Brg1-overexpressing (CMV-Brg1) mice and wild-type (WT) C57BL/6 mice underwent HIR. Lung histology, oxidative injury markers, and antioxidant enzyme concentrations in the lung were assessed. The protein expression levels of Brg1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in the lung were analyzed by Western blotting. Results In the WT group, histopathological analysis revealed that lung damage peaked at 6 h after HIR. Meanwhile, the lung reactive oxygen species (ROS) and 8-isoprostane levels were significantly increased. The protein expression of Brg1 in lung tissue decreased to a minimum at 6 h. Overexpression of Brg1 alleviated lung injury and decreased the amounts of oxidative products, including the levels of 8-isoprostane and ROS, as well as the percentage of positive cells for 4-hydroxynonenal (4-HNE) and 8-oxo-2′-deoxyguanosine (8-OHdG). Brg1 overexpression increased the expression and nuclear translocation of Nrf2 as well as activated the antioxidases. In addition, it decreased the expression of inflammatory factors. Conclusion Overexpression of Brg1 alleviates oxidative lung injury induced by HIR, likely through the Nrf2 pathway.

Highlights

Hepatic ischemia/reperfusion injury (HIRI) occurs in many surgeries, including liver transplantation, liver resection, and cardiovascular surgery [1, 2]
We demonstrated that hepatic ischemia/reperfusion (HIR) can induce remote acute lung injury (ALI) accompanied by a significant increase of oxidative damage and a significant decrease of Brahma-related gene-1 (Brg1) expression
We revealed that overexpression of Brg1 attenuated lung injury after HIR, promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and attenuated oxidative stress by activating the antioxidase system including heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), superoxide dismutase (SOD), Glutamate-Cysteine Ligase Catalytic Subunit (GCLC), and GSTα1

Summary

Introduction

Hepatic ischemia/reperfusion injury (HIRI) occurs in many surgeries, including liver transplantation, liver resection, and cardiovascular surgery [1, 2]. We have reported previously that up to 58.2% of patients developed pulmonary complications after liver transplantation; among them, 27.5% suffered from an acute lung injury (ALI) [5, 6]. Given that numerous risk factors are involved in ALI induced by hepatic ischemia/reperfusion (HIR), effective and preventive strategies are needed [7, 8]. Multiple factors are reported to take part in the pathogenesis of post-HIR ALI [9]. Excessive reactive oxygen species (ROS) produced in the liver after ischemia/reperfusion is one of the main mechanisms involved in HIR-induced ALI [10,11,12]. Clearance of ROS appears to be a potential therapeutic strategy for post-HIR ALI

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Discussion

Conclusion