Effect of c-Jun NH2-Terminal Kinase Signal Transduction Pathway on Hyperoxia-Induced Lung Injury in Rats

Objective To explore the effect of c-Jun NH2-terminal kinase(JNK)signal transduction pathway on hyperoxia-induced lung injury in rats.Methods Twenty-four Wistar rats aged 3 weeks were randomly divided into 3 groups(n=8):room-air control group,7 d hyperoxia exposure group,and 7 d hyperoxia exposure with inhibitor of JNK intervention group.The rats in hyperoxia exposure group were exposed to high concentration of oxygen [fractional concentration of inspired oxygen(FiO2)≥950 mL·L-1] at normal pressure.The rats in room-air control group were placed in room air(FiO2=210 mL·L-1)at normal pressure.The rats in JNK inhibitor intervention group were intraperitoneally injected 30 mg·kg-1 SP600125 and exposed to hyperoxia 2 h later.The histopathological changes of lung tissues were observed by means of light microscope,therefore the changes of lung W/D weight ratio,total protein in bronchoalveolar lavage fluid(BALF)and lung permeation index were detected.The extent of lung cells apoptosis was analyzed by terminal deoxynucleotidyltrans-ferase-mediated dUTP nick end labeling assay.The protein level of p-JNK was measured by Western blotting analysis.Results Compared with room-air control group,conspicuous hyperaemia,edema,hemorrhage and extensive inflammation cells infiltration in the lung tissues were significantly observed in 7 d hyperoxia exposure group.The lung W/D weight ratio,total protein in BALF,lung permeation index,cell apoptotic index and the p-JNK protein levels of lung tissues all significantly increased in 7 d hyperoxia exposure group compared with those in room-air control group(Pa0.05).The apoptosis cells were evident in alveolar epithelial cells,distal bronchiolar epithelium and endothelial cells.The histopathological injury of lung tissues,inflammatory effusion,edema were significantly decreased,and the lung W/D weight ratio,total protein in BALF,lung permeation index,cell apoptotic index and the p-JNK protein levels of lung tissues all reduced markedly in 7 d hyperoxia exposure with inhibitor of JNK intervention group compared with those in 7 d hyperoxia exposure group(Pa0.05).Conclusions The activation of JNK signal transduction pathways may initiate under hyperoxia stress and may play a role in promoting inflammation and cells apoptosis in hyperoxia-induced lung injury.Inhibition of JNK signal transduction pathway may be protective for hyperoxia-induced lung injury.