OBJECTIVETo investigate the molecular mechanism of tanshinone II A (TSN) for preventing left ventricular hypertrophy (LVH) by studying the expressions of angiotensin I type 1 receptor (AT1R), transforming growth factor beta1 (TGF-beta1) and intracellular signal protein gene (Smads gene) in the hypertrophic myocardium of hypertensive rat models induced by pressure over-loading.

METHODSSD rat model of LVH was established by abdominal aorta constriction. The model animals were randomly divided into 4 groups 4 weeks after modeling, the untreated model control group (C1), the two tested groups (T1 and T2) treated respectively with high (20 mg/kg) and low (10 mg/kg) dose of TSN II A per day via intraperitoneal injection, and the positive control group (C2) treated with 10 mg/kg of Valsartan per day by gastric perfusion, with 8 animals in each group. Besides, 8 SD rats managed with sham operation were set up as the sham-operated control group (C3) After an 8-week treatment, the caudal arterial pressure, left ventricular mass index (LVMI), myocardial fiber dimension (MFD, by pathologic examination with HE staining) in rats were measured. Meanwhile, mRNA expression of AT1R, protein expression of TGF-beta1 and activity of Smad-3, 4, 7 in the ventricular tissue were detected by RT-PCR analysis and Western blotting respectively.

RESULTS(1) Blood pressure in Group T1 and T2 was unchanged after treatment, which was significantly higher than that in Group C2 and C3 (P < 0.01, P < 0.05). (2) LVMI and MFD in Group T1, T2 and C2 were higher than that in Group C3 (P < 0.01), but remarkably lower than that in Group C1 (P < 0.01). (3) Levels of AT1R, TGF-beta1 and Smad-3 expression increased significantly in the model rats (P < 0.01), but they were down-regulated in Group T1 and C2, and the TGF-beta1 regulating effect in the C2 was more potent than that in Group T1 and T2 (P < 0.05). (4) Protein expression of Smad-7 was up-regulated in Group T1, T2 and C2 obviously (P < 0.01), and the effect in Group T1 was superior to that in C2 (P < 0.05).

CONCLUSIONThe myocardial hypertrophy inhibition effect of TSN II A is a blood pressure independent process, and it may be related to the inhibition of AT1R mRNA expression and blocking of TGF beta1/Smads signal pathway.