The Effect of TanshinoneⅡ A upon the TGF-beta1/Smads Signaling Pathway in Hypertrophic Myocardium of Hypertensive Rats

To investigate the molecular mechanism by which TanshinoneⅡA(TSNⅡA)prevents left ventricular hypertrophy(LVH),we examined the expression of AT1R,TGF-β1 and Smads gene in the hypertrophic myocardium of hypertensive rats with abdominal aorta constriction.LVH model was established by creating abdominal aorta constriction.Four weeks later,animals were randomly divided into 4 groups with 8 animals in each.One group was used as model control,the other three groups were treated with TSNⅡA(20 mg/kg),TSNⅡA(10 mg/kg)and valsartan(10 mg/kg),respectively.Another 8 SD rats were subjected to sham surgery and served as blank control.After 8-week treatment,the caudal artery pressure of the animals was measured.The tissues of left ventricle were taken for the measurement of the left ventricular mass index(LVMI)and pathological sectioning and HE-staining were used for determining the myocardial fiber dimension(MFD).The mRNA expression of AT1R,protein expression of TGF-beta1 and activity of Smad-2,4,7 were detected by RT-PCR and Western blotting,respectively.Our results showed that(1)the blood pressure of rats treated with TSNⅡA,either at high or low dose,was significantly higher than those in the control and valsartan-treated group(P<0.01,P<0.05);(2)LVMI and MFD in TSNⅡA and valsartan-treated rats were higher than those in the control group(P<0.05)but significantly lower than those in the model control(P<0.01);(3)the high doses of TSNⅡA and valsartan significantly down-regulated the mRNA expression of AT1R and protein expression of TGF-beta1 and Smad-3 in the hypertrophic myocardium(P<0.01),and TGF-beta1 in valsartan-treated animals was more significantly lower than that in rats treated with TSNⅡA;(4)the two doses of TSNⅡA and valsartan significantly up-regulated the protein expression of Smad-7 in the hypertrophic myocardium(P<0.01),and Smad-7 in the animals treated with high-dose TSNⅡA was significantly higher than that in rats treated with valsartan.It is concluded that inhibition of myocardial hypertrophy induced by TSNⅡA independent of blood pressure.The underlying mechanism might be the down-regulated expression of AT1R mRNA and Smad-3,increased production of Smad-7,and blocking effect of TSNⅡA on TGF beta1/Smads signal pathway in local myocardium.