Department of Biochemistry, College of Integrated Chinese and Western Medicine, Hebei Medical University, Hebei, People's Republic of China; Department of Surgery, First Hospital of Hebei Medical University, Hebei, People's Republic of China.
Department of Biochemistry, College of Integrated Chinese and Western Medicine, Hebei Medical University, Hebei, People's Republic of China.
Tissue Cell. 2023 Apr;81:102031. doi: 10.1016/j.tice.2023.102031. Epub 2023 Jan 20.
The O subfamily of forkhead (FoxO) 1 may participate in the pathogenesis of diabetic microvascular endothelial injury. However, it is unknown whether D-beta-hydroxybutyrate (BHB) regulates cardiac microvascular endothelial FoxO1 to play protective roles in diabetes. In the study, limb microvascular morphological changes, endothelial distribution of the tight junction protein Claudin-5 and FoxO1, and FoxO1 content in limb tissue from clinical patients were evaluated. Then the effects of BHB on cardiac microvascular morphological changes, cardiac FoxO1 generation and its microvascular distribution in diabetic rats were measured. And the effects of BHB on FoxO1 generation in high glucose (HG)-stimulated human cardiac microvascular endothelial cells (HCMECs) were further analyzed. The results firstly confirmed the enhanced limb microvascular FoxO1 distribution, with reduced Claudin-5 and endothelial injury in clinical patients. Then the elevated FoxO1 generation and its enhanced cardiac microvascular distribution were verified in diabetic rats and HG-stimulated HCMECs. However, BHB inhibited the enhanced cardiac FoxO1 generation and its microvascular distribution with attenuation of endothelial injury in diabetic rats. Furthermore, BHB reduced the HG-stimulated mRNA expression and protein content of FoxO1 in HCMECs. In conclusion, BHB reduced the enhanced cardiac microvascular endothelial FoxO1 to play protective roles in diabetic rats and HG-stimulated HCMECs.
叉头框蛋白 O 亚家族 1（FoxO1）可能参与糖尿病微血管内皮损伤的发病机制。然而，目前尚不清楚 D-β-羟丁酸（BHB）是否调节心脏微血管内皮 FoxO1，以在糖尿病中发挥保护作用。在研究中，评估了临床患者肢体微血管形态变化、紧密连接蛋白 Claudin-5 和 FoxO1 的内皮分布以及肢体组织中 FoxO1 的含量。然后测量了 BHB 对糖尿病大鼠心脏微血管形态变化、心脏 FoxO1 生成及其在心脏微血管中的分布的影响。并进一步分析了 BHB 对高糖（HG）刺激的人心血管内皮细胞（HCMECs）中 FoxO1 生成的影响。结果首先证实了临床患者肢体微血管 FoxO1 分布增加，Claudin-5 减少和内皮损伤。然后在糖尿病大鼠和 HG 刺激的 HCMECs 中证实了 FoxO1 生成的增加及其心脏微血管的分布增强。然而，BHB 抑制了糖尿病大鼠心脏 FoxO1 生成及其微血管分布的增加，减轻了内皮损伤。此外，BHB 降低了 HG 刺激的 HCMECs 中 FoxO1 的 mRNA 表达和蛋白含量。总之，BHB 通过降低增强的心脏微血管内皮 FoxO1 发挥保护作用，在糖尿病大鼠和 HG 刺激的 HCMECs 中发挥作用。
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