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
Objective:To study the effect of tanshinoneⅡA on the cell signal transduction system protein kinase B(Akt) in rats with hypertrophy of the myocardium induced by partial constriction of the thoracic aorta. Methods:Rat models of myocardial hypertrophy were established by the thoracic aorta partial constriction method. Forty-eight rats were randomly divided into the sham-operative group,the model group,the valsartan treatment group,and the low-,medium-,and high-dose tanshinone treatment groups.The heart mass index(HMI),left ventricular mass index(LVMI),ejection fraction(EF),left ventricular posterior wall(LVPW),and interventricular septal thickness(IVS) were detected by high-frequency ultrasonography.The myocardial fiber diameter(MFD) was detected by HE staining,and the contents of p-Akt and p-Gsk3βin the myocardium were detected by Western blot.Results:Compared with the sham-operative group,the levels of HMI,LVMI,LVPW,IVS,and MFD were increased respectively in the other groups(P<0.05);the contents of p-Akt and p-Gsk3βwere also increased in the other groups.Compared with the model group,the levels of HMI,LVMI,LVPW,IVS,and MFD were decreased respectively in all treatment groups(P<0.05);the contents of p-Akt and p-Gsk3βwere decreased in all treatment groups as well.There was no significant difference,however,among the low-,medium-,and high-dose tanshinone treatment groups and the valsartan treatment group(P>0.05).Conclusion:TanshinoneⅡA can prevent myocardial hypertrophy by its action on the protein kinase B(Akt) signaling pathway.
<正>Objective:To investigate the effects of sodium tanshinoneⅡA sulfonate(STS)on the hypertrophy induced by angiotensinⅡ(AngⅡ)in primary cultured neonatal rat cardiac myocytes. Methods:The effect of STS on cytotoxicity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-3,5- phenytetrazoliumromide(MTT)assay.As indexes for cardiocyte hypertrophy,cell size was determined by phase contrast microscopy and protein synthesis rate was measured by ~3H-leucine incorporation. The proto-oncogene c-fos mRNA expression of cardiocytes was assessed using reverse transcription polymerase chain reaction(RT-PCR).Results:STS could inhibit cardiocyte hypertrophy,increase the protein synthesis rate,and enhance proto-oncogene c-fos mRNA expression in cardiocytes induced by AngⅡ(P<0.01),with an effect similar to that of Valsartan,the AngⅡreceptor antagonist.Conclusion:STS can prevent the hypertrophy of cardiac myocytes induced by AngⅡ,which may be related to its inhibition of the expression of proto-oncogene c-fos mRNA.
