Mei He , Weiguang Luo , Shuwei Ning , Yuexin Yu , Bin Yang , Zhikun Guo
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引用次数: 0
Abstract
Objective
Beta-hydroxybutyrate (BHB) has been demonstrated to enhance cardiac function in patients with diabetic cardiomyopathy (DCM), the underlying mechanism remains unclear.
Methods
A DCM rat model was established, BHB was administered via intraperitoneal injection. The therapeutic effects of BHB were assessed based on cardiac function, fasting glucose levels, myocardial fibrosis markers and myocardial macrophage polarization. To elucidate the mechanism of action, co-culture experiments were conducted using cardiac fibroblasts and peritoneal macrophages to evaluate collagen expression in fibroblasts and macrophage polarization under BHB treatment.
Results
BHB improved cardiac function in DCM rats, reduced fasting glucose levels, alleviated cardiac fibrosis and modulated macrophage polarization. After BHB treatment, the proportion of M1 macrophages decreased while that of M2 macrophages increased in the myocardium of DCM rats. Cardiac fibroblasts isolated from neonatal rats, when co-cultured with peritoneal macrophages under high-glucose conditions, exhibited altered macrophage polarization and collagen expression. High-glucose conditions promoted an increase in M1 macrophages and a decrease in M2 macrophages. BHB treatment reversed this trend by reducing M1 macrophages and promoting M2 macrophage polarization.
Conclusions
We show that BHB mitigates cardiac fibrosis in DCM rats by promoting M2 macrophage polarization. BHB may be a useful therapeutic approach for DCM treatment.
期刊介绍:
Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.