The roles of cytokines and water sodium channel proteins in acute kidney injury-induced acute lung injury rats

Abstract

Objective To observe the physiopathologic changes of lung in rats with acute ischemic kidney injury,and to study the roles of cytokine,epithelial sodium channel protein (ENaC) and aquaporin 1 (AQP1) in acute lung injury brought on by acute ischemic kidney injury in rats.Methods A total of 60 healthy male Wistar rats (300-320 g) were randomly (random number) divided into control groups (group A,n =30) and acute kidney injury group (group B,n =30).The model of acute ischemic kidney injury in rats was made by bilateral renal arteiovenous blockage with clamps.Six rats of each group were sacrificed at 0,2,4,6 and 8 hours after modeling.Lung tissue of rats was harvested and stained with hematoxylin-eosin (HE) staining method,and the pathological changes of lung were observed under microscope.The ratio of wet and dry weight (W/D) of lung was calculated.The levels of protein in bronchoalveolar lavage fluid (BALF) were measured.The levels of IL-6 and TNF-α both in serum and BALF were tested.The concentrations of AQP1 and α-ENaC in lung were measured.Results At six hours after modeling,the pH value of arterial blood of rats in group B began to get lowered compared to group A.There was no difference in partial pressure of oxygen in arterial blood between two groups during entire period of experiment (P ＞0.05).Protein level in BALF and W/D of lung increased significantly two hours after modeling in rats of group B (P ＜ 0.05).The histopathological changes of acute lung injury including swollen aleolar epithelium,widened interalveolar septum,edema of alveoli and alveolar interstitium,alveolar neurophil sequestration,erythrocytes and protein in exudates were observed.The levels of TNF-α and IL-6 in serum and in BALF began to increase at two hours after modeling.The levels of AQP1 and α-ENaC of lung in rats with acute kidney injury decreased gradually and were lower than those in rats of group A (P ＜0.05).Conclusions Aleolar epithelial-endothelial barrier function was already compromised at the beginning of AKI,suggesting the acute lung injury was already brought on.The levels of TNF-α,IL-6 in serum and in BALF increased after the occurrence of acute kidney injury.The decreases in lung AQP1 and α-ENaC might contribute to the lung injury caused by early acute kidney injury. Key words: Acute kidney injury; Acute lung injury; Cytokine; Aquaporin 1; Epithelial sodium channel protein