Aim To investigate the regulatory role of sphingosine-1-phosphate receptors(S1PR) in cardiomyocyte hypertrophicresponse induced by S1P.Methods Cellvolumes and protein compound rate of neonatal heart cells were used as indexs of hypertrophic cardiomyocytes models induced by S1P.Neonatal heart cells were randomly divided into 5 groups: normal control;hyperrophic group: cells were stimulated by S1P(1000 nmol/L);pretreatment group: cells were treated with VPC23019(10 μmol/L) 30 min before adding S1P;pretreatment group: cells were treated with JTE(10 μmol/L) 30 min before adding S1P and pretreatment group: cells were treated with Staurosporine(10 nmol/L) 30 min before adding S1P.Protein compound rate of neonatal rat cardiomyocyte cells was assayed by -leucine incorporation.The expression of β-myosin heavy chain(β-MHC) was detected by qPCR and Western Blot.Results 10,100 and 1000 nmol/L S1P increased neonatal rat cardiac cell volume and -leucine incorporation,especially 1000 nmol/ L S1P.Cells treated with S1P at 1000 nmol/L for 48 h were chosen as hypertrophic cardiocyte model.S1P(1000 nmol/L) treatment of myocytes 48 h,can increase significantly -leucine incorporation,the effect was significantly inhibited by S1P2 receptor inhibitor(JTE) or protein kinase C(PKC) inhibitor(Staurosporine).Compared with the con-trol group,hypertrophy of myocardial cells of β-MHC mRNA and protein levels were significantly increased.Compared with S1P(1000 nmol/L) treatment group,β-MHC expression levels of S1P2 receptor-specific inhibitor and the PKC inhibitor group was significantly decreased.Conclusion The activation of S1P2 played an important role in cardiomyocytes hypertrophy induced by S1P.S1P2-PKC signaling regulates the cardiomyocyte hypertrophic responses induced by S1P.