Aerobic exercise inhibited cardiac Hmox-1/GPX4 mediating ferroptosis to alleviate cardiac remodeling in diabetic cardiomyopathy
WANG Ting1, 2, ZOU Yan3, LI Haiyan4, WANG Yonghua3
1.Department of Ultrasound, Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, China; 2.Department of Cardiology, the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015, China; 3.Department of Physical Education, Wenzhou Medical University, Wenzhou 325035,China; 4.Department of Rehabilitation, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China
WANG Ting,ZOU Yan,LI Haiyan, et al. Aerobic exercise inhibited cardiac Hmox-1/GPX4 mediating ferroptosis to alleviate cardiac remodeling in diabetic cardiomyopathy[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(5): 370-378.
Abstract：Objective: To illuminate the protective effect of aerobic exercise inhibiting ferroptosis by heme oxygenase-1 (Hmox-1) and glutathione peroxidase 4 (GPX4) against diabetic myocardial remodeling. Methods:Male C57BL/6 mice (as control) and db/db mice were fed with ordinary diet, which were spontaneously induced with type 2 diabetes, and mice fed with high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes mice were treated with 12 weeks treadmill training. Then, cardiac function was examined by echocardiography HE, Masson’s staining and Sirius staining were respectively used to measure cardiac fibrosis andmorphology. In addition, mRNA and protein of GPX4 and Hmox-1 levels were detected by real-time quantitative polymerase chain reaction or Western blot. And cardiac 4-HNE was detected by immunohistochemical method. Results:Compared with the controls, both the heart of db/db mice and HFD+STZ induced mice presented by increased cardiac Hmox-1 and 4-HNE expression, decreased cardiac GPX4 level, accompanied by a reduction of cardiac dysfunction and cardiac hypertrophy and fibrosis. However, these abnormal changes were reversed by aerobic exercise, reflected by improved cardiac function, downregulated Hmox-1 and 4-HNE level, markedly activated GPX4 (P<0.05). Conclusion: Aerobic exercise inhibited cardiac ferroptosis to reverse cardiac remodeling in diabetic mice.
