Effects of genistein on Nrf2/HO-1 pathway in myocardial tissues of diabetic rats / 中南大学学报(医学版)

ABSTRACT

To investigate the effects of genistein (Gen) on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in myocardial tissues of diabetic rats.
 Methods: Thirty-two male SD rats were randomly divided into 4 groups: a normal control (NC) group, a diabetic control (DM) group, a low-dose Gen treatment (L-Gen) group, and a high-dose Gen treatment (H-Gen) group (n=8). Intraperitoneal injection of streptozotocin was utilized to induce diabetic rat model. After the establishment of diabetic model, the rats in L-Gen and H-Gen groups were intragastric administration with 10 and 50 mg/kg Gen solution. Following 8 weeks, the left ventricular hemodynamic parameters and fasting blood glucose (FBG) levels were measured. The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in myocardial tissue were determined. The ultrastructure of myocardium was observed under transmission electron microscopy. The expression of HO-1 at mRNA level in myocardial tissue was detected by RT-PCR. The protein levels of Nrf2 and HO-1 in myocardial tissue were detected by Western blotting. 
 Results: Compared with the NC group, left ventricular systolic pressure (LVSP), maximal rise/fall rate of left ventricular pressure (±dp/dtmax), and the levels of GSH-Px, SOD and CAT were decreased (all P<0.01), while the left ventricular end-diastolic pressure (LVEDP), FBG and MDA were increased (all P<0.01) in the DM group. The myocardial ultrastructure was obviously damaged, and the expressions of myocardial Nrf2 and HO-1 were significantly decreased (both P<0.01) in the DM group. Compared with the DM group, there was no difference in FBG in the L-Gen group, while ±dp/dtmax and LVSP were significantly increased (all P<0.05), and LVEDP and MDA were decreased (P<0.05 or P<0.01), and the levels of GSH-Px, SOD and CAT were increased (P<0.05 or P<0.01) in the L-Gen group. The myocardial ultrastructure damage was alleviated and the expressions of Nrf2 and HO-1 were increased (both P<0.01) in the L-Gen group. Compared with L-Gen group, the aforementioned indexes were improved in the H-Gen group (P<0.05 or P<0.01).
 Conclusion: Genistein exerted antioxidant effects on myocardial injury in diabetic rats, and the mechanisms might be related to regulating the Nrf2/HO-1 pathway and enhancing the activities of antioxidant enzymes in myocardial tissues.