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Resveratrol mitigates diabetes-induced cardiac dysfunction via SIRT1/PPAR-α/PGC-1 pathway
1Department of Geriatric, The Third Hospital of Hebei Medical University, No. 139 Ziqianlu Road, Shijiazhuang, 050051, Hebei, China.
Abstract:
Diabetic cardiomyopathy (DCM) significantly contributes to cardiovascular complications in diabetes. This study investigated the protective effects of Resveratrol (RES) in combination with evidence-based nursing on DCM and the underlying molecular mechanisms. Eighty elderly patients with type 2 diabetes mellitus (T2DM) and DCM were randomly assigned to a control group or an RES group. The RES group received RES (800 mg/day) along with evidence-based nursing, while the control group received a placebo with nursing care for six months. Clinical indicators, including glucose and lipid metabolism, lactate dehydrogenase (LDH) activity, inflammatory markers, and cardiac function parameters, were evaluated. Additionally, T2DM rat models were used to examine oxidative stress, cells proliferation, fats accumulation, mitochondrial dysfunction, apoptosis and autophagy, while high glucose (HG)-induced H9C2 myocardial cells were used to investigate cellular mechanisms involving the SIRT1/PPAR-α/PGC-1 pathway. RES combined with evidence-based nursing improved glucose and lipid metabolism, reduced LDH activity, decreased inflammatory markers (TNF-α, IL-6), and enhanced cardiac function in T2DM patients with DCM. In rats, RES restored left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) while reducing myocardial apoptosis with lower Bax and cleaved caspase-3 levels and higher Bcl-2 expression, reduced fibrosis and fat accumulation. Additionally, RES alleviated oxidative stress by decreasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, suppressed myocardial apoptosis, improved mitochondrial function while increasing ATP and superoxide dismutase (SOD) activity as well as enhancing autophagy. SIRT1 inhibitor (EX527) injections in rats reversed the beneficial effects of RES. In HG-treated H9C2 cells, RES improved cell viability, reduced apoptosis, alleviated oxidative stress and enhanced autophagy. RES ameliorates DCM through SIRT1/PPAR-α/PGC-1 signaling pathway in rats and improves efficacy of elderly DM patients in combination with evidence-based care.
Insights
Resveratrol (RES) combined with evidence-based nursing protects against diabetic cardiomyopathy (DCM) by improving metabolic health and cardiac function. This intervention targets oxidative stress and apoptosis via the SIRT1/PPAR-α/PGC-1 pathway.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Diabetic cardiomyopathy (DCM) is a major cardiovascular complication in type 2 diabetes mellitus (T2DM).
- Existing treatments for DCM have limitations, necessitating novel therapeutic strategies.
- Resveratrol (RES) shows potential cardioprotective effects, but its combination with nursing interventions requires further investigation.
Purpose of the Study:
- To investigate the protective effects of Resveratrol (RES) combined with evidence-based nursing on diabetic cardiomyopathy (DCM) in elderly patients with T2DM.
- To elucidate the underlying molecular mechanisms of RES in ameliorating DCM using animal and cellular models.
- To evaluate the impact of the combined intervention on clinical indicators and cardiac function.
Main Methods:
- Eighty elderly T2DM patients with DCM were randomized into a control group (placebo + nursing) or an RES group (RES 800 mg/day + nursing) for six months.
- T2DM rat models were used to assess myocardial protection, oxidative stress, apoptosis, autophagy, and fibrosis.
- High glucose (HG)-induced H9C2 myocardial cells were utilized to explore cellular mechanisms involving the SIRT1/PPAR-α/PGC-1 pathway.
Main Results:
- The RES group showed improved glucose and lipid metabolism, reduced lactate dehydrogenase (LDH) activity, and decreased inflammatory markers (TNF-α, IL-6).
- In rats, RES improved cardiac function (LVEF, LVFS), reduced myocardial apoptosis and fibrosis, alleviated oxidative stress (ROS, MDA), and enhanced mitochondrial function and autophagy.
- In vitro, RES improved H9C2 cell viability, reduced apoptosis, and alleviated oxidative stress, with effects reversed by a SIRT1 inhibitor (EX527).
Conclusions:
- Resveratrol combined with evidence-based nursing demonstrates significant protective effects against diabetic cardiomyopathy in elderly T2DM patients.
- The therapeutic benefits are mediated through the SIRT1/PPAR-α/PGC-1 signaling pathway, involving modulation of oxidative stress, apoptosis, and mitochondrial function.
- This combined approach offers a promising strategy for managing diabetic cardiomyopathy and improving cardiovascular outcomes in diabetic patients.
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