Author + information
- Gan Shouyi1,
- Hui Yu1,
- Hong-xia Huang1,
- Bing Li1,
- Ling-Yong Zeng1,
- Xiong Ge1,
- Jun Huang1,
- Guang-rui Feng1,
- Liang Liu1,
- Fei Cai3 and
- Cai-rong Li2
- 1Department of cardiovascular medicine, Xianning Central Hospital, The First Affiliated Hospital Of Hubei University Of Science And Technology, Jing
- 2Department of medicine, Hubei University of Science and Technology, Xianning, China
- 3Department of pharmacology, Hubei University of Science and Technology, Xianning, China
Diabetic cardiomyopathy, characterized by the presence of diastolic and/or systolic myocardial dysfunction, is one of the major causes of heart failure. Hyperglycemia leads to upregulation of reactive oxygen species (ROS) and inflammatory condition that may contribute to diabetic cardiomyopathy. Resveratrol has been shown as a promising experimental agent in cardiac I/R due to its effect on cellular energy metabolism, oxidative stress, and inflammation. A biologically active resveratrol analogues, RSVA314, We hypothesized that RSVA314 would attenuate diabetic cardiomyopathy (DCM).The purpose of this study was to investigate whether RSVA314 exerts the therapeutic effect on streptozotocin-induced DCM in rats.
A high-fat diet and low-dose streptozotocin administration were used to induce type 2 diabetes in Wistar rats. Diabetic rats were treated with RSVA314 for 16 weeks. At the end of this study, after cardiac function measurements were performed, rats were sacrificed and their hearts were harvested for further histologic and molecular biologic analysis. Cardiac tissue was analyzed by ELISA for the protein content of the cytokines TNF-alpha, IL-6, IL-1beta, and TGF-beta. Phosphorylation of AMP was analyzed by western blot, and the total cardiac collagen content was analyzed by Sirius red staining.
RSVA314 treatment ameliorated cardiac dysfunction in the DCM group, as shown by the result of echocardiography and hemodynamic measurements. Administration of RSVA314 did not affect plasma glucose and insulin levels or body weights in STZ-induced diabetic rats, but normalized myocardial steatosis.
The levels of malondialdehyde (MDA) in plasma and myocardium in RSVA314 -treated group were significantly lower than those in diabetic control group. RSVA314 reduced IL-1 beta but increased TNF- alpha and IL-6 levels in the diabetic cardiomyopathy. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic cardiac tissues. RSVA314 treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group.
Our study indicates that treatment with RSVA314 mitigates cardiac dysfunction and interstitial fibrosis, and these beneficial of RSVA314n may belong to the suppression of oxidative stress injury and regulatingproinflammatory cytokines, partially via activation of AMPK protein.
Key words: RSVA314; Diabetic cardiomyopathy; oxidative stress; proinflammatory cytokines; AMP-activated protein kinase[Acknowledgements] This work was supported by the Foundation from Department of Education of Hubei Province (D20162803), Health and Family Planning Commission of Hubei Province(WJ2015Z122) and the Foundation from Hubei University of Science and Technology(LCZX201515).