Effect of genistein on myocardial fibrosis in diabetic rats and its mechanism.

The aim of the present study was to investigate the effects of genistein (GEN) on myocardial fibrosis in type 1 diabetic rats and explore the underlying mechanisms. Rats were divided into 4 groups: Normal control (N), diabetic control (D), low‑dose GEN treatment (L) and high‑dose GEN treatment (H) groups. Following 8 weeks, the ventricular hemodynamic parameters, fasting blood glucose (FBG), heart‑weight to body‑weight ratio (HW/BW), myocardial hydroxyproline (Hyp) content, serum creatine kinase MB isozyme (CK‑MB), lactate dehydrogenase (LDH), tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β) and interleukin‑6 (IL‑6) levels were measured. The histomorphology and ultrastructure of the heart were observed. The protein expression of myocardial transforming growth factor‑β1 (TGF‑β1), mothers against decapentaplegic homolog (Smad)‑3, phosphorylated (p)‑Smad3, Smad4, collagen‑I and collagen‑III were estimated. Compared with the N group, while the cardiac function was decreased, the levels of FBG, HW/BW, Hyp content, CK‑MB, LDH, TNF‑α, IL‑1β and IL‑6 were increased in the D group. The myocardial histomorphological alterations and ultrastructure were damaged, and the protein expression of myocardial TGF‑β1, Smad3, p‑Smad3, Smad4, collagen‑I and collagen‑III were increased in the D group. Compared with the D group, there were no differences in the ventricular hemodynamic parameters, FBG and p‑Smad3 expression in the L group, while HW/BW, Hyp content, CK‑MB, LDH, TNF‑α, IL‑1β and IL‑6 levels were decreased. The myocardial histomorphological damage was alleviated and the protein expression of TGF‑β1, Smad3, Smad4, collagen‑I and collagen‑III was decreased in the L group. Compared with L group, excluding FBG, the aforementioned indices were improved in the H group. In conclusion, GEN can attenuate myocardial fibrosis in type 1 diabetic rats, and the underlying mechanisms may be associated with the reduction of CK‑MB and LDH leakage, inhibition of the inflammatory reaction, and suppression of the TGF‑β1/Smad3 signaling pathway to regulate collagen expression.