甘酸通过通过TLR4/MyD88/NF-κB信号通路抑制巨细胞M1极化来缓解动脉样硬化
Ya-Zhu Quan1, Ang Ma2, Chao-Qun Ren1
1State Key Laboratory of Vascular Homeostasis and Remodeling, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Atherosclerosis
|February 28, 2024
概括
来自Ganoderma lucidum的甘酸 (GA) 抑制动脉样硬化发展,并通过通过TLR4/MyD88/NF-κB通路减少M1巨细胞极化来改善斑块稳定性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
背景情况:
- 动脉样硬化 (AS) 是一种由脂质积累和斑块形成驱动的慢性炎症性疾病.
- 来自Ganoderma lucidum的甘酸 (GA) 具有不同的药理特性.
- 了解GA的抗动脉样硬化机制对于治疗开发至关重要.
研究的目的:
- 为了评估甘酸 (GA) 的抗动脉样硬化作用.
- 阐明GA在预防AS的基础药理机制.
- 为了研究GA对AS巨细胞两极分化的影响.
主要方法:
- ApoE-/-小鼠通过高胆固醇饮食诱导AS并接受GA治疗.
- 网络药理学预测了抗动脉样硬化路径.
- 在体外研究中使用骨髓衍生的巨细胞 (BMDMs) 和RAW264.7细胞来评估巨细胞极化和信号通路.
主要成果:
- GA治疗显著抑制了AS的进展,通过减少大动脉斑块大小和死核,提高了斑块稳定性,并增加了原蛋白含量.
- GA降低了M1巨细胞在斑块中的比例,并在体外抑制了M1极化,降低了CD86+巨细胞和促炎细胞因子 (IL-6,IL-1β,MCP-1).
- GA的机制涉及调节TLR4/MyD88/NF-κB信号通路以抑制M1巨细胞的两极化.
结论:
- 甘酸 (GA) 显示出显著的抗动脉样硬化作用,改善了斑块的稳定性.
- GA 抑制M1巨细胞的两极分化,这是AS病变发生的关键因素.
- GA的抗动脉样硬化作用部分通过TLR4/MyD88/NF-κB信号通路进行介导.
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