Cardioprotective effects of polydatin against myocardial injury in HFD/stz and high glucose-induced diabetes via a Caveolin 1-dependent mechanism.

BACKGROUND

Diabetic cardiomyopathy (DCM) is defined as cardiac dysfunction involving changes in structure, function, and metabolism in the absence of coronary artery disease, which eventually developed into heart failure. There is still a lack of effective drugs for the treatment of DCM, while the ameliorative effects of traditional herbs on DCM have been commonly reported. Polydatin (PD) is a glucoside derivative of traditional herbs of resveratrol, which has been shown to ameliorate the pathological development of DCM. However, the cardioprotective effect and mechanism of PD in the improvement of myocardial injury are still unclear.

AIM OF STUDY: This study aimed to investigate the cardio-protective role of PD on DCM and reveal the critical effect of Cav1 in PD' regulation of DCM.

MATERIALS AND

METHODS

The Cav1-/- and Cav1+/+mice and H9C2 cells were used to induce DCM models and then given PD treatment (150 mg/kg) or not. The cardiac functions of all mice were checked via echocardiography, and myocardial histological changes were measured by H&E, periodic acid-schiff (PAS) and Masson staining. The markers expression of heart fibrosis and inflammation, and hypertrophic factors were detected using western blotting. The NF-κB signaling activation was performed by confocal, immunohistochemical, Electrophoretic mobility shift assay (EMSA) and western blotting.

RESULTS

Here, we found that PD significantly improved the cardiac function and injury of diabetic Cav1+/+ mice, and enhanced the expression of Cav1 in the cardiac tissues of diabetic Cav1+/+ mice and HG-induced H9C2 cells. Further investigation showed that when Cav1 was knocked down, PD no longer plays the cardioprotective effect and inhibits the NF-κB signaling pathway activation in HFD/stz-treated diabetic mice and HG-induced H9C2 cells.

CONCLUSION

These results demonstrated that PD inhibited the hyperglycemia-induced myocardial injury and inflammatory fibrosis of DCM models in vivo and in vitro, and targeting Cav1 may provide a novel understanding the mechanism of the treatment of PD in DCM.