Effects of tanshinone II on the mRNA expression of c-fos、c-myc and c-jun in angiotensin II-induced hypertrophy of cardiomyocytes

Aim To investigate the effect of tanshinoneⅡA(TSN) on the hypertrophy induced by angiotensinⅡ(AngⅡ)in the primary culture of neonatal rat cardiomyocytes. Methods Cardiomyocytes of Wistar rats were cultured with pancreatin and preplating technique. The hypertrophy of cardiomyocytes was induced with angiotensinⅡ, and intervened with TanshinoneⅡA and Valsartan. The effect of TSN on cardiomyocytewas evaluated by 3-[4,5-dimethylthiazol-2-yl]-3,5-diphenylformazan (MTT) assay. As the index of cardiomyocyte hypertrophy, protein synthesis rate was measured by ~3H-Leucine incorporation and the cell size was determined by phase contrast microscope. The proto-oncogene c-fos、c-myc and c-jun mRNA expressions were assessed using reverse transcription polymerase chain reaction (RT-PCR). Results Exposure of cultured cardiomyocytes to TSN (5～80 μmol·L~ -1 ) for 24 h produced marginal cytotoxicity. Additonally, myocyte monolayers continued to contract synchronously in the presence of TSN. With the treatment of cardiomyocytes by AngII for 7 days, the cell size of cardiomyocytes of the group of Ang Ⅱ(28.5±3.8) μm increased more prominently than the group of control(19.8±1.9) μm(P0.05). TSN could restrained the increase of cardiomyocyte size(21.3±2.5) μm which was induced by Ang Ⅱ(28.5±3.8) μm(P0.05); with the treatment of cardiomyocytes by Ang Ⅱ for 24 h, the cardiomyocyte protein synthesis rate of the group of Ang Ⅱ(1900±100) cpm increased more prominently than the group of control(1205±129) cpm,(P0.01). TSN and Valsartan had no effect on cardiomyocyte protein synthesis, but it could restrained the increase of cardiomyocyte protein synthesis rate (P0.01), which was induced by Ang Ⅱ. Ang Ⅱ was added to the culture medium and 30 min later c-fos、c-myc and c-jun mRNA expressions of cardiomyocyte increased evidently(P0.01). If TSN or Valsartan was added before that ,they could inhibit the effect of Ang Ⅱ (P0.01)after they were in effect for 30 min. Nevertheless TSN and Valsartan had no effect on the express of c-fos、c-myc and c-jun mRNA. Conclusions TSN can prevent the hypertrophy of cardiomyocytes induced by Ang Ⅱ, which may relate to the decreased expressions of proto-oncogene c-fos , c-myc and c-jun mRNA by TSN.