D-β-Hydroxybutyrate脱酶通过激活Nrf2缓解糖尿病诱导的动脉样硬化
Jie Lin1,2,3,4, Qian Ren1,2,3,4, Fanjie Zhang1,2,3,4
1Department of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical University, Luzhou, China.
Thrombosis and haemostasis
|July 3, 2023
概括
β-基酸脱酶1 (Bdh1) 降低了糖尿病相关动脉样硬化的氧化应激和炎症. 它对Nrf2通路的激活可以防止细胞损伤和疾病进展.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 代谢疾病 代谢疾病
背景情况:
- 动脉样硬化 (AS) 是一种慢性炎症性疾病.
- 糖尿病通过增加巨细胞的氧化压力而加剧AS.
- 在这个过程中Beta-hydroxybutyrate脱酶1 (Bdh1) 的作用尚不清楚.
研究的目的:
- 研究Bdh1在调节糖尿病诱导的AS中巨细胞氧化应激中的作用和机制.
- 在正常患者,AS患者和糖尿病诱导的AS患者中确定Bdh1表达水平.
主要方法:
- 股骨动脉的免疫组织化学分析.
- 使用糖尿病Apoe-/-小鼠和高葡萄糖 (HG) 处理的Raw264.7巨细胞.
- 使用腺相关病毒 (AAV) 介导的Bdh1操纵 (过度表达/沉默).
主要成果:
- 在糖尿病诱导的AS患者,巨细胞和小鼠中观察到Bdh1表达的减少.
- 在糖尿病小鼠中,Bdh1过度表达减弱了大动脉斑块形成.
- 沉默Bdh1增加了巨细胞中的ROS产生和炎症,N-乙半氨酸可以逆转这种情况.
- 通过抑制ROS,Bdh1过度表达保护巨细胞免受HG诱导的细胞毒性.
- Bdh1通过烟酸激活了Nrf2通路,减少了氧化应激.
结论:
- Bdh1通过促进体代谢,加速脂质降解和降低脂质水平来减轻糖尿病Apoe-/-小鼠中的AS.
- Bdh1通过调节烟酸代谢流量来激活巨细胞中的Nrf2通路,从而抑制氧化应激.
- 这导致ROS和炎症因子的产生减少,为糖尿病相关的AS提供了潜在的治疗点.
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