Methane Inhalation Protects Against Lung Ischemia-Reperfusion Injury in Rats by Regulating Pulmonary Surfactant via the Nrf2 Pathway.

Bing Zhang,Xuan Wang,Chao Meng,Yanwei Yin,Junmin Yu,Guangqi Li,Han Zhao,Xiaojun Tian

doi:10.3389/fphys.2021.615974

Abstract

Methane (CH4) exerted protective effects against lung ischemia-reperfusion (I/R) injury, but the mechanism remains unclear, especially the role of pulmonary surfactant. Therefore, this study aimed to explore the effects of CH4 inhalation on pulmonary surfactant in rat lung I/R injury and to elucidate the mechanism. Rats were randomly divided into three groups (n = 6): the sham, I/R control, and I/R CH4 groups. In the sham group, only thoracotomy was performed on the rats. In the I/R control and I/R CH4 groups, the rats underwent left hilum occlusion for 90 min, followed by reperfusion for 180 min and ventilation with O2 or 2.5% CH4, respectively. Compared with those of the sham group, the levels of large surfactant aggregates (LAs) in pulmonary surfactant, lung compliance, oxygenation decreased, the small surfactant aggregates (SAs), inflammatory response, oxidative stress injury, and cell apoptosis increased in the control group (P < 0.05). Compared to the control treatment, CH4 increased LA (0.42 ± 0.06 vs. 0.31 ± 0.09 mg/kg), oxygenation (201 ± 11 vs. 151 ± 14 mmHg), and lung compliance (16.8 ± 1.0 vs. 11.5 ± 1.3 ml/kg), as well as total antioxidant capacity and Nrf2 protein expression and decreased the inflammatory response and number of apoptotic cells (P < 0.05). In conclusion, CH4 inhalation decreased oxidative stress injury, inflammatory response, and cell apoptosis, and improved lung function through Nrf2-mediated pulmonary surfactant regulation in rat lung I/R injury.

Highlights

Lung ischemia-reperfusion (I/R) injury can occur during many clinical events, such as lung transplantation, cardiopulmonary bypass, pulmonary embolism, single-lung ventilation, resuscitation for circulatory arrest, and shock, and can contribute to severe organ failure and increased mortality in patients (Tejwani et al, 2016; Saito et al, 2019)
Oxidative stress injury is an important factor contributing to lung I/R injury, leading to the intracellular generation of reactive oxygen species (ROS) (Boros and Keppler, 2019)
We found that Nuclear factor E2related factor 2 (Nrf2) exerted antioxidant effects against lung I/R injury in a rat lung transplantation model (Meng et al, 2017)

Summary

Introduction

Lung ischemia-reperfusion (I/R) injury can occur during many clinical events, such as lung transplantation, cardiopulmonary bypass, pulmonary embolism, single-lung ventilation, resuscitation for circulatory arrest, and shock, and can contribute to severe organ failure and increased mortality in patients (Tejwani et al, 2016; Saito et al, 2019). Lung I/R injury is a complex pathological process that includes oxidative stress injury, the inflammation response, and cell apoptosis and is characterized by poor oxygenation, tissue edema, and neutrophil infiltration (den Hengst et al, 2010). Oxidative stress injury is an important factor contributing to lung I/R injury, leading to the intracellular generation of reactive oxygen species (ROS) (Boros and Keppler, 2019). The accelerated generation of ROS is a major cause of cell apoptosis and inflammation and exacerbates lung injury during the ischemia and reperfusion phase (Yang et al, 2019). We found that Nrf exerted antioxidant effects against lung I/R injury in a rat lung transplantation model (Meng et al, 2017). The Nrf pathway may be a crucial mechanism in lung I/R injury

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