Abstract:Objective:To investigate the effect of simvastatin at different concentrations on the proliferation and paracrine functions of BMSCs in vitro and explore its possible mechanism. Methods:BMSCs were isolated from Sprague-Dawley rats and expanded by whole bone marrow adherence culture method. Cells of 3 passage,which were at logarithmic phase,were used in experiment. BMSCs were cultured in serum-free medium for 12 hours,then incubated with various concentrations of simvastatin for 24 hours. The influences of simvastatin on BMSCs’ proliferation were assayed with CCK-8 assay,and their mRNA expressions of vascular endothelial growth factor(VEGF) and Hepatocyte growth factor(HGF) were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Besides,Western-blot used to investigate the pAkt and Akt expressions in BMSCs. Results:Simvastatin in a certain range of concentration (0.001 μmol/L ~0.100 μmol/L) significantly increased proliferation and paracrine (VEGF and HGF) functions of BMSCs in vitro(P < 0.01). Simvastatin at 0.01 μmol/L concentration reached the maximum effects on the proliferation and paracrine functions of BMSCs. While the concentrations of simvastatin were more than 0.01 μmol/L,the improvement effects showed a tendency to decline. Simvastatin at 1.000 μmol/L concentration had no significant effect on promoting proliferation of BMSCs,but significantly increased the VEGF and HGF mRNA expression compared with that of the control group. Both pAKt expression and pAKt/AKt ratio in BMSCs were significantly higher than those in the control group after 0.01 μmol/L simvastatin treatment(P < 0.01). Conclusion:Simvastatin in a certain concentration range could improve BMSCs’ proliferation and paracrine capabilities,and the Akt pathway might be involved in the mechanism.