Clinical & Experimental Cardiology
Open Access

Abstract

Dapagliflozin Protects Cardiomyocytes from H/R Injury by Regulating miR-124-3p

Kaiyuan Cen, Xianglong Liang, Yuan Ding, Haibo Yu*

Background: Reperfusion therapy is one of the main methods for alleviating myocardial infarction. However, this treatment may cause injury to the myocardium, known as Hypoxia/Reoxygenation (H/R) injury. Dapagliflozin is a kind of novel hypoglycemic drug, but its role in modulating the H/R injury of cardiomyocytes has not been fully clarified.

Methods: The H/R model and MI rats were established. Reactive Oxygen Species (ROS) level was examined by 2’, 7’- Dichlorofluorescein-Diacetate (DCFH-DA) assay. The release of Lactate Dehydrogenase (LDH) and Creatine Kinase- MB (CK-MB) were examined by enzyme-linked immunosorbent assay. Cell viability was measured by MTT assay and the cell apoptosis was validated by flow cytometry. MicroRNA-124-3p (miR-124-3p), Signal Transducer and Activator of Transcription 3 (STAT3), Phosphoinositide 3-Kinase (PI3K), phospho-PI3 Kinase (p-PI3K) and phosphorylation- STAT3 (p-STAT3) expressions were measured by quantitative Real-Time PCR (qRT-PCR) or Western blot. Besides, dual-luciferase reporter gene assay was performed to confirm the interaction between miR-124-3p and STAT3. Echocardiography was performed to assess cardiac function.

Results: Dapagliflozin could greatly decrease the levels of ROS, LDH and CK-MB, promote cell viability and inhibit the apoptosis; dapagliflozin up-regulated miR-124-3p expression and down-regulated STAT3, p-STAT3 and inactivate the PI3K/AKT pathway. miR-124-3p inhibition or STAT3 overexpression counteracted the effects of dapagliflozin on ROS, LDH and CK-MB levels and the viability and apoptosis of AC16 cardiomyocytes. Dapagliflozin treatment reduced the dilatation and contractile dysfunction of left ventricle in MI rats.

Conclusion: Dapagliflozin protects cardiomyocytes from H/R injury through modulating miR-124-3p/STAT3 and PI3K/AKT axis, suggesting it may be a promising drug for treating heart ischemia-reperfusion injury.

Published Date: 2025-09-10; Received Date: 2024-08-09