Author:
Li Fan,Hu Zhenfei,Huang Yidan,Zhan Haiting
Abstract
Abstract
Objective
Dexmedetomidine (DEX) has been shown to have anti-apoptotic effects in diabetes mellitus, but its role in mitigating diabetic cardiomyopathy (DCM) through ferroptosis regulation is unclear.
Methods
An in vitro DCM model was established using H9C2 cells induced with high glucose (HG) and treated with DEX at varying doses and a nuclear factor erythroid 2-realated factor 2 (Nrf2) specific inhibitor ML385. Cell viability was evaluated using the MTT method after treatment with DEX or mannitol (MAN), and the dosage of DEX used in subsequent experimentation was determined. The effects of HG-induced high osmotic pressure were assessed using MAN as a control. Cell apoptosis was evaluated using flow cytometry. Protein levels of Bcl2, Bax, nuclear Nrf2, and glutathione peroxidase 4 (GPX4) were measured using Western blot. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, Fe2+ concentration and reactive oxygen species (ROS) levels were measured using corresponding kits and dichlorodihydrofluorescein diacetate, respectively.
Results
Treatment with DEX or MAN had no effect on H9C2 cell viability. HG induction reduced H9C2 cell viability, increased cell apoptosis, upregulated levels of Bax, Fe2+, MDA, and ROS, and downregulated Bcl2 protein levels, SOD activity, and protein levels of nuclear Nrf2 and GPX4. DEX inhibited HG-induced H9C2 cell apoptosis, promoted Nrf2 nuclear translocation, and activated the Nrf2/GPX4 pathway. Inhibition of Nrf2 partially reversed the protective effects of DEX against HG-evoked H9C2 cell injury.
Conclusion
Our findings demonstrate that DEX attenuates HG-induced cardiomyocyte injury by inhibiting ferroptosis through the Nrf2/GPX4 pathway, providing potential therapeutic targets for DCM treatment.
Funder
Natural Science Foundation Project of Xinjiang Uygur Autonomous Region.
Publisher
Springer Science and Business Media LLC
Subject
Cardiology and Cardiovascular Medicine,General Medicine,Surgery,Pulmonary and Respiratory Medicine
Cited by
1 articles.
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1. Ironing out the details: ferroptosis and its relevance to diabetic cardiomyopathy;American Journal of Physiology-Regulatory, Integrative and Comparative Physiology;2023-12-01