Ac-SDKP Regulates The Activation Of Senescence-Related Signals On Alveolar Type Ⅱ Epithelial Cells In Silicotic Rats

Objective To observe the regulatory effect of N-acetyl-serine-aspartyl-lysine-proline（Ac-SDKP）on the senescence related signal of alveolar type Ⅱ epithelial cells in the process of silicosis fibrosis and its mechanism.Methods HOPE-MED8050 dynamic silica dust exposure control system was applied in the establishment of a rat silicosis model,and the experimental silicosis rats were divided into control group,silicosis group and Ac-SDKP post-treatment group.MLE-12 cells were cultured in vitro,and the experimental cells was divided into control group,Si O₂ induction group,Ac-SDKP group and Si O₂+Ac-SDKP group.Sirius red staining was used to observe the collagen deposition in lung tissue,immunofluorescence staining was used to detect the location of p21;immunoblotting was used to detect the expression of type I collagen（Col I）,p-capillary dilatation ataxia mutant kinase（p-ATM）,p-p53,p21,p16,p-capillary dilation ataxia（p-ATR）.Results Compared with the control group,the lung tissue of rats in the silicosis group formed typical silicon nodules with collagen deposition,immunofluorescence staining results showed that p21 protein was mainly localized in alveolar type Ⅱ epithelial cells,immunoblotting results showed that Col I,p-ATM,p-p53,p21,p16,p-ATR protein expression levels were up-regulated in lung tissue;compared with the silicosis group,the number and area of silicon nodules in the lungs of the Ac-SDKP post-treated group were significantly reduced,and the protein expression levels of Col I,p-ATM,p-p53,p21,p16,p-ATR protein in the lung tissue were decreased（P<0.05）.Compared with the control group,the protein levels of Col I,p-ATM,p-p53,p21,p-ATR and p16 protein in MLE-12 cells of the Si O₂-induced group were up-regulated;compared with the Si O₂-induced group,the expression levels of Col I,p-ATM,p-p53,p21,p16,p-ATR protein were down-regulated in the Si O₂+Ac-SDKP group（P<0.05）.Conclusion Ac-SDKP can inhibit the activation of senescence-related signals of alveolar type Ⅱ epithelial cells,and then play its role in antagonizing silicosis fibrosis in rats.Figure 9;Table 7;Reference 187...