Tanshinone IIA has definite protective effects on various
cardiovascular diseases. However, in
hypertension-induced
left ventricular hypertrophy (H-LVH), the signaling pathways of
tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-
clip induced hypertensive rats (n = 32) were randomized to receive
tanshinone IIA (5, 10, 15 mg/kg per day) or 5%
glucose injection (GS).
Sham-operated rats (n = 8) received 5%GS as control. Cardiac function and dimensions were assessed by using an echocardiography system. Histological determination of the
fibrosis and apoptosis was performed using
hematoxylin eosin, Masson's trichrome and TUNEL staining.
Matrix metalloproteinase 2 (MMP2) and tissue inhibitor of
matrix metalloproteinases type 2 (TIMP2)
protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related
proteins impact on cardiac
fibrosis and apoptosis. Compared with the
sham rats, the heart tissues of H-LVH (5%GS) group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM) deposition. In the H-LVH group,
tanshinone IIA treated decreased
malondialdehyde (MDA) content and increased
superoxide dismutase (SOD) activity.
Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of
Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma
apelin level increased with down-regulation of APJ receptor.
Tanshinone IIA suppressed cardiac
fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-β/Smads signaling pathway activity. In conclusion, our in vivo study showed that
tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM deposition, and limiting apoptosis of cardiomyocytes and oxidative damage.