Simvastatin attenuates hypoxia-reoxygenation injury of alveolar type II cells by activating PI3K/Akt pathway

Abstract

Objective To investigate the protective effects and the mechanisms of simvastatin (SIM) preconditioning on hypoxia and reoxygenation injury of alveolar type Ⅱ ( AT Ⅱ ) cells.Methods Human AT Ⅱ cells-derived ceil line A549 cells were cultured in vitro,and CoCl2 was used to establish the hypoxia and reoxygenation injury model on AT Ⅱ cells.A 549 cells were treated with various concentrations of simvastatin (5-100 μmol/L).The proliferation of AT Ⅱ cells was evaluated by cell counting Kit-8 (CCK-8) assay.The cell apoptosis assay was performed by Hoechst 33342 staining under the fluorescence microscopy.The protein levels of SP-C,Akt,P70,mTOR and Caspase-3 were detected by using Western blotting.Results As compared with the control group,pretreatment with low dose (5-20 μmol/L) of simvastatin markedly reduced apoptosis of A549 cells,and increased their proliferation.Also,protein levels of SP-C,p-Akt,p-P70 and mTOR were significantly increased,but Caspase-3 level was decreased (P ＜0.01).Administration of PI3K inhibitor wortmannin could competitively reverse the protective effect of simvastatin (P ＜ 0.01 ).Conclusion Simvastatin could protect AT Ⅱ cells against CoC12-indμced hypoxia and reoxygenation injury,which was at least partially mediated by activation of intracellular PI3K/Akt pathway. Key words: Simvastatin; PI3K/Akt pathway; Alveolar type Ⅱ cells; Hypoxia and reoxygenation injury