Reversion of hypoxta and reoxygenation injury of alveolar type Ⅱ cells by simvastatin / 中华胸心血管外科杂志

ABSTRACT

Objective To investigate the protective effects of simvastatin on cobalt choride ( CoCl2 ) -induced hypoxia and reoxygenation injury on alveolar type Ⅱ cells and the underlying mechanisms.Methods CoCl2 was used to establish the hypoxia and reoxygenation injury model on AT Ⅱ cells.Blank,control and variant doses simvastatin-treated groups ( 5,10,20,30,50,100 μ mol/L) were designed in the present study.The proliferation of AT Ⅱ cells was evaluated by Cell Counting Kit-8 ( CCK-8 ) assay.The percentage of apoptotic cells was assessed by flow cytometry AV/PI double-staining.The protein levels of surfactant protein-C (SP-C) and proliferating cell nuclear antigen (PCNA) in AT Ⅱ cells was determined by Western blot.Results As compared with the control group,pretreatment with low dose (5 - 20 μmol/L),but not high dose simvastatin (50 - 100 μmol/L) markedly reduced A549 cells apoptosis,and increased their proliferation and the protein levels of SPC and PCNAin vitro.The protective effect could be reversed in vitro by L-mevalonate,a simvastatin competitive inhibitor,which indicated that the inhibition of mevalorate pathway was involved in the simvastatin induced AT Ⅱ cells function restoration.Condusion Low doses simvastatin reversed CoCl2-induced hypoxia and reoxygenation injury of AT Ⅱ cells.The inhibition of mevalonate pathway contributed to simvastatin induced AT Ⅱ cells function restoration.