β-羟基丁酸通过Nox2/GSK-3β增加调节性T细胞减轻射血分数保留的心力衰竭
β-Hydroxybutyrate Mitigated Heart Failure with Preserved Ejection Fraction by Increasing Treg Cells via Nox2/GSK-3β.
作者信息
Liao Shengen, Tang Yuan, Yue Xin, Gao Rongrong, Yao Wenming, Zhou Yanli, Zhang Haifeng
机构信息
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, People's Republic of China.
Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215002, People's Republic of China.
出版信息
J Inflamm Res. 2021 Sep 16;14:4697-4706. doi: 10.2147/JIR.S331320. eCollection 2021.
BACKGROUND
This study was designed to investigate the cardioprotective role of β-hydroxybutyrate (BHB) in heart failure with preserved ejection fraction (HFpEF) and the underlying mechanism.
METHODS
A two-hit model with a high-fat diet (HFD) and N-nitrol-arginine methyl ester (L-NAME) was used as an HFpEF model. The treatment group received a weekly intraperitoneal injection of β-hydroxybutyrate (BHB). Cardiac function, inflammation, and fibrosis were evaluated. CD3CD4Foxp3 positive cells within the myocardium were quantified by flow cytometry. The NADPH oxidase 2 (NOX2)/glycogen synthase kinase-3β (GSK3β) pathway was examined by immunoblot analysis.
RESULTS
BHB improved diastolic function, fibrosis and cardiac remodeling in HFpEF. Additionally, BHB inhibited cardiac inflammation and increased cardiac Treg cells, which could be due to the downregulation of the NOX2/GSK-3β pathway.
CONCLUSION
BHB protected against the progression of HFpEF by increasing cardiac Treg cells by modulating the NOX2/GSK-3β pathway.
背景
本研究旨在探讨β-羟基丁酸（BHB）在射血分数保留的心力衰竭（HFpEF）中的心脏保护作用及其潜在机制。
方法
采用高脂饮食（HFD）和N-硝基-L-精氨酸甲酯（L-NAME）的双打击模型作为HFpEF模型。治疗组每周腹腔注射β-羟基丁酸（BHB）。评估心脏功能、炎症和纤维化。通过流式细胞术对心肌内CD3CD4Foxp3阳性细胞进行定量。通过免疫印迹分析检测NADPH氧化酶2（NOX2）/糖原合酶激酶-3β（GSK3β）途径。
结果
BHB改善了HFpEF的舒张功能、纤维化和心脏重塑。此外，BHB抑制心脏炎症并增加心脏调节性T细胞，这可能是由于NOX2/GSK-3β途径的下调。
结论
BHB通过调节NOX2/GSK-3β途径增加心脏调节性T细胞，从而保护HFpEF的进展。
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