[Regulating effect of N-acetyl-seryl-aspartyl-lysyl-proline on activation of c-jun N-terminal kinase pathway in rats with silicosis].

Objective To investigate the regulatory effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the activation of c-jun N-terminal kinase (JNK) signal transduction pathway and its role in silicotic fibrosis.Methods A rat model of silicosis was developed by intratracheal instillation.Sixty rats were randomly divided into 4-week control group (n=10),8-week control group (n=10),4-week silicosis model group (n=10),8-week silicosis model group (n=10),AcSDKP treatment group (n=10),and AcSDKP prevention group (n=10).The content of hydroxyproline in lung tissue was measured using a p-dimethylaminobenzaldehyde reagent; the expression levels of transforming growth factor (TGF)-beta 1 (TGF-β1),phospho-JNK,JNK,and c-jun in lung tissue were measured by Western blot.The lung fibroblasts from neonatal rats were cultured,and the 4th generation of cells were used in the experiment; these cells were divided into control group,TGF-β1 stimulation group,SP600125 intervention group,and AcSDKP intervention group.The distributions of phospho-JNK and c-jun in lung fibroblasts were observed by immunocytochemistry; the expression levels of type Ⅰ collagen and type Ⅲ collagen in lung fibroblasts were measured by Western blot.Results The expression levels of TGF-β13 phospho-JNK,and c-jun and the content of hydroxyproline in the AcSDKP treatment group were 70.60％,78.03％,79.85％,and 71.28％,respectively,of those in the 4-week silicosis model group (P＜0.05) and 77.99％,66.73％,69.94％,and 64.82％,respectively,of those in the 8-week silicosis model group (P＜0.05); the expression levels of TGF-β1,phospho-JNK,and c-jun and the content of hydroxyproline in the AcSDKP prevention group were 84.56％,61.18％,64.73％,and 74.96％,respectively,of those in the 8-week silicosis model group (P＜0.05).The expression levels of phospho-JNK and c-jun in the AcSDKP intervention group were 54.59％ and 55.56％,respectively,of those in the TGF-β1 stimulation group; the expression levels of type Ⅰ collagen and type Ⅲ collagen in the AcSDKP intervention group were 79.9％ and 84.4％,respectively,of those in the TGF-β1 stimulation group (P＜0.05).Conclusion AcSDKP exerts anti-silicotic fibrosis effect probably by inhibiting the activation of JNK signal transduction pathway mediated by TGF-β1 and the deposition of interstitial collagen. Key words: N-acetyl-seryl-aspartyl-lysyl-proline; Transforming growth factor-β1; Silicosis; Hydroxyproline; Collage