The influence of src kinase/signal transducer and activator of transcription on lipopolysaccharide-induced acute lung injury in rats

Abstract

Objective To investigate the role of Src/STAT signal pathway in LPS-induced ALI. Methods Sixty male SD rats were divided into four groups using a random number table:blank (NS) group,lipopolysaccharide (LPS) group,LPS+SU6656 (LPS+SU) group and NS+SU6656 (NS+SU) group.The concentrations of macrophage inflammatory protein 2(MIP-2) and interleukin (IL)-6 in bronchoalveolar lavage fluids (BALF) were detected by ELISA and the histopathologic changes of lung tissues were observed by hematoxylin-eosin (H-E) staining.The expression of nuclear factor kappa B(NF-κB) in nuclear extracts,phosphor-STAT and IκBα in cytoplasmic extracts were analyzed by Western blot.In addition,survival rate with the other 10 rates each group was investigated. Results The serious pulmonary inflammation and conspicuous lung damage were observed in LPS group.AS compared with LPS group,the MIP-2 and IL-6 in BALF were significantly decreased [MIP-2 reached a peak at 6 h,(1 135±209) vs (875±112),P＜0.05.IL-6 reached a peak at 3 h,(2 235±267) vs(5 125±658 ),P＜0.05].The histopathologic changes of lung tissues were relieved obviously.Wet / dry weight ratio of the lung was decreased.LPS+SU6656 group had a higher survival rate (37.6％ vs 10.5％,P＜0.05) and the NF-κB activation and the degradation of IκBα in cytoplasma were inhibited. Conclusions These data suggested that Src/STAT signal pathway plays an essential role in LPS -induced acute lung injury.SU6656,Src kinase specific inhibitor,attenuates LPS-induced lung injury via inhibiting the NF-κB activation and IκBoα degradation,indicating that the Src/STAT signal pathway may be involved in the activation of NF-κB. Key words: Src kinase/signal transducer and activator of transcription signal pathway; Lipopolysaccharide; Acute lung injury; Nuclear factor kappa B; SU6656; Macrophage inflammatory protein 2; Interleukin-6