NaHS Alleviated Cell Apoptosis and Mitochondrial Dysfunction in Remote Lung Tissue after Renal Ischemia and Reperfusion via Nrf2 Activation-Mediated NLRP3 Pathway Inhibition.

Guangning Zhao,Long Yang,Liming Li,Zhongqiang Fan,Vasiliki Galani

doi:10.1155/2021/5598869

Abstract

Objective Acute kidney injury (AKI) is a common and severe complication in critically ill patients, often caused by renal ischemia-reperfusion (RIR). Previous studies have confirmed that lung injury, rather than renal injury, is one of the leading causes of AKI-induced death. The pathophysiological mechanisms of acute lung injury (ALI) resulting from AKI are very complex and remain unclear. In the present study, we aimed to explore the protective effects and potential mechanism of sodium hydrosulfide (NaHS) on lung injury in RIR mice. Methods The RIR model was established in wild-type and Nrf2−/− mice. Different groups of mice were treated with NaHS and MCC950. Lung tissues were harvested to detect lung injury, mitochondrial function, cell apoptosis, the NLRP3 inflammasome, and Nrf2 pathway-related molecules. Results RIR led to a deterioration in lung histology, the wet/dry weight ratio, PaO2/FiO2, and mitochondrial function, in addition to stimulating the activation of the NLRP3 and Nrf2 pathways. MCC950 alleviated mitochondrial dysfunction, lung apoptosis, and histology injury in the lungs after RIR. NaHS treatment markedly improved the lung histological scores, the wet/dry weight ratio, bronchoalveolar lavage fluid (BALF) cell counts, BALF neutrophil counts, BALF neutrophil elastase activity, BALF protein concentration, PaO2/FiO2, mitochondrial morphology, the red/green fluorescence intensity that indicates changes in mitochondrial membrane potential, respiratory control rate (RCR), ATP, reactive oxygen species (ROS) release, and cell apoptosis via Nrf2-mediated NLRP3 pathway inhibition. Conclusion NaHS protected against RIR-induced lung injury, mitochondrial dysfunction, and inflammation, which is associated with Nrf2 activation-mediated NLRP3 pathway inhibition.

Highlights

Acute kidney injury (AKI) is a common and severe complication in critically ill patients, often caused by renal ischemiareperfusion (RIR) [1]
The results of hematoxylin and eosin (H&E) staining showed that compared with the control (Con) group, renal ischemia reperfusion (RIR) led to severe lung injury with almost complete destruction of the pulmonary architecture, alveolar space disappearance, infiltration of neutrophils into lung interstitium and alveolar space, and interstitial edema
RIR induced a significant upregulation in lung histological scores when compared with the Con group, which was reduced by NaHS administration (Figure 1(b), P < 0:05)

Summary

Introduction

Acute kidney injury (AKI) is a common and severe complication in critically ill patients, often caused by renal ischemiareperfusion (RIR) [1]. The mortality rate of AKI patients is 5.5-fold higher than that of non-AKI patients [2]. The mortality rate of AKI is much higher when combined with extrarenal distal organ injury. Improving renal function by renal replacement therapy alone does not reduce AKI-related mortality, which is mainly due to damage to distal organs. Previous studies have confirmed that lung injury, rather than renal injury, is one of the leading causes of death induced by AKI [3, 4]. Many clinicians have insisted that patients often die from dysfunction of other organs accompanied by AKI rather than from AKI itself [2]. There has been no effective medicine or methods for treating AKI

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Results

Conclusion