Quercetin Ameliorates Myocardial Injury in Diabetic Rats by Regulating Autophagy and Apoptosis through AMPK/mTOR...

Area of Science:

• Cardiovascular Research
• Metabolic Disorders
• Cellular Biology

Background:

• Diabetes mellitus (DM) is associated with high-glucose environments that exacerbate myocardial injury.
• Diabetic cardiomyopathy involves disrupted autophagy and increased apoptosis.
• Quercetin (QUE) is a flavonoid with potential therapeutic properties.

Purpose of the Study:

• To investigate the regulatory effects of QUE on autophagy and apoptosis in diabetic myocardial injury.
• To elucidate the molecular mechanisms underlying QUE's cardioprotective effects in a type 2 DM rat model.

Main Methods:

• Type 2 DM rat models were induced using streptozotocin (STZ) and a high-carbohydrate (HC) diet.
• Evaluated myocardial structure, collagen deposition, PAS-positive cells, and apoptosis.
• Assessed autophagy markers (LC3, Beclin1, P62) and apoptosis markers (Caspase-3, Bax/Bcl-2) via Western blotting and immunoprecipitation (IP).
• Measured blood pressure, blood glucose, cardiac function, and oxidative stress.

Main Results:

• Diabetic rats exhibited increased blood glucose, blood pressure, cardiac hypertrophy, myocardial fibrosis, apoptosis, and oxidative stress.
• Autophagy was significantly reduced, evidenced by decreased LC3 and Beclin1 and increased P62.
• QUE treatment improved cardiac function, reduced hyperglycemia and hypertension, alleviated oxidative stress, and restored autophagy by inhibiting Beclin1-Bcl-2 binding.
• QUE treatment decreased apoptosis by modulating Bax/Bcl-2 expression.

Conclusions:

• Quercetin (QUE) effectively suppresses diabetic myocardial injury and ameliorates cardiac function in type 2 DM rats.
• QUE exerts its cardioprotective effects by enhancing myocardial autophagy and inhibiting apoptosis, primarily through the AMPK/mTOR signaling pathway.
• QUE's mechanism involves modulating the interaction between Beclin1 and Bcl-2, thereby promoting autophagy.