H3 relaxin ameliorates mitochondrial quality control and apoptosis in cardiomyocytes of type 2 diabetic rats via activation of the AMPK pathway.

PURPOSE: This study aims to explore the protective mechanism of H3 relaxin treatment for type 2 diabetic cardiomyopathy, focusing on its effects on the mitochondrial quality control system and cardiomyocyte apoptosis.

METHODS

A type 2 diabetes rat model was induced with a high-fat diet and streptozotocin. The treatment group received H3 relaxin for 2 weeks. In cellular studies, H9C2 cardiomyocytes were treated with high glucose and palmitic acid, followed by H3 relaxin, MFN2 lentivirus, and AMPK inhibitor compound C. Mitochondrial quality control, membrane potential, ROS, and apoptosis markers were assessed.

RESULTS

H3 relaxin improved apoptosis markers, reduced mitochondrial fission (Drp1, Fis1) and mitophagy proteins (parkin, PINK1), and increased mitochondrial fusion proteins (MFN2, OPA1). It restored mitochondrial membrane potential, lowered ROS, and showed anti-apoptotic effects dependent on MFN2. AMPK pathway activation by H3 relaxin was crucial, as compound C largely negated these benefits.

CONCLUSION

H3 relaxin improves the mitochondrial quality control system and reduces high glucose and palmitic acid-induced apoptosis by upregulating MFN2. This protective effect is achieved through the activation of the AMPK pathway.