The purpose of the present study was to evaluate whether tanshinone IIA (TIIA) could treat cardiac dysfunction and fibrosis in heart failure (HF) by inhibiting oxidative stress. An HF model was induced by ligation of the left anterior descending artery to cause ischemia myocardial infarction (MI) in Sprague‑Dawley rats. Cardiac fibrosis was evaluated using Masson's staining, and the levels of collagen I, collagen III, TGF‑β, α‑smooth muscle actin (α‑SMA), matrix metalloproteinase (MMP) 2 and MMP9 were determined using PCR or western blotting. TIIA treatment reversed the decreases of left ventricular (LV) ejection fraction, fractional shortening (FS), LV systolic pressure and the maximum of the first differentiation of LV pressure (LV ± dp/dtmax), the increases of LV volume in systole, LV volume in diastole, LV end‑systolic diameter and LV end‑diastolic diameter in MI rats. TIIA administration also reversed the increases of expression levels of collagen I, collagen III, TGF‑β, α‑SMA, MMP2 and MMP9 in the heart of MI rats and in angiotensin (Ang) II‑treated cardiac fibroblasts (CFs). TIIA reversed the decreases of superoxide dismutase activity and malondialdehyde and the increases of superoxide anions and NADPH oxidase (Nox) activity in both MI rats and Ang II‑treated CFs. Nox4 overexpression inhibited the effects of TIIA of improving cardiac dysfunction and fibrosis in MI rats and Ang II‑treated CFs. These results demonstrated that TIIA improved cardiac dysfunction and fibrosis via inhibiting oxidative stress in HF rats. Nox4 could regulate the inhibitory effects of TIIA on HF and cardiac fibrosis.
Keywords: tanshinone IIA; heart failure; myocardial infarction; oxidative stress; fibrosis.