Abstract: ObjectiveTo study the effects of simvastatin on the hypertrophy of cultured rat cardiac myocytes induced by serum and investigate the role of phosphoinositide 3-kinase（PI3K）/protein kinase B（PKB）.MethodsImage analysis system was used to measure cell surface area.Protein synthesis of myocytes derived from cultured neonatal Sprague-Dawley（SD） was measured via -leucine incorporation.The expression level of mRNA of atrial natriuretic peptide（ANP）in myocytes was determined with reverse transcription polymerase chain reaction（RT-PCR）.RT-PCR and Western blot were used to study the mRNA and protein expression level of PKB.Rlllesults（1）Cardiac myocytes surface area was lowered in serum-free group than in 15% serum group （538.04±118.60）μm 2 vs （1611.16±160.75）μm 2（P＜0.01）.Simvastatin decreased cell surface area in a concentration dependent manner.Cell surface area in 10 -5 and 10 -6 mol/L simvastatin groups were （799.84±167.70）μm 2 and （1076.88±199.28）μm 2, which were both significantly lower than that in serum group（both P＜0.01）.（2） Incorporation rate of serum-free group was （1305±92）cpm/well .It was much higher in serum group（2369±106）cpm/well than that in serum-free group（P＜0.01）.Incorporation rate of -leucine in 10 -5 and 10 -6 mol/L simvastatin groups were （1 707±101）cpm/well and （1 962±125）cpm/well, respectively, which were both lower than that in serum group（P＜0.01）.（3）With the increase of simvastatin concentrations, the ANP mRNA expression was decreased gradually compared with that of serum group（0.60±0.03）.The level of ANP mRNA in 10 -5 and 10 -6 mol/L simvastatin groups were 0.29±0.03 and 0.40±0.03, which were both lower than that in serum group（P＜0.01）.（4）Simvastatin inhibited the expression of PKB mRNA induced by serum in a concentration dependent manner.The PKB mRNA expression level in serum group was 0.51±0.03.The PKB mRNA level in 10 -5 and 10 -6 mol/L simvastatin groups were 0.28±0.02 and 0.36±0.03, respectively, which were both much lower than that of serum group（P＜0.01）.Similarly, compared with serum group（60.80±3.49）, the protein level of PKB in 10 -5 and 10 -6 mol/L simvastatin groups （42.41±2.83 and 45.68±3.43） were also both significantly decreased（P＜0.01）.ConclusionSimvastatin inhibit the hypertrophy of cultured rat cardiac myocytes induced by serum.The mechanism might be related with the decrease of expression level of PKB.