基础医学与临床 ›› 2024, Vol. 44 ›› Issue (3): 368-373.doi: 10.16352/j.issn.1001-6325.2024.03.0368

• 研究论文 • 上一篇    下一篇

抑制髓样细胞触发受体-1(TREM-1)减轻慢性间歇性低氧诱发的模型小鼠动脉粥样硬化

余晗俏1*, 李超1, 余育斌1, 冯丽娜2, 盛晓生1, 叶晓霞1, 王林燕1   

  1. 1.金华市人民医院 心内一科,浙江 金华 321000;
    2.金华市金东区第二人民医院 全科医学科,浙江 金华 321000
  • 收稿日期:2023-11-09 修回日期:2024-01-02 出版日期:2024-03-05 发布日期:2024-02-22
  • 通讯作者: *:yuhanqiao1990@163.com
  • 基金资助:
    浙江省中医药科技计划项目(2022Z@075)

Inhibition of triggering receptor expressed on myeloid cells-1(TREM-1) attenuates chronic intermittent hypoxia-induced atherosclerosis in mouse models

YU Hanqiao1*, LI Chao1, YU Yubin1, FENG Lina2, SHENG Xiaosheng1, YE Xiaoxia1, WANG Linyan1   

  1. 1. Department of Cardiology, Jinhua People ′s Hospital, Jinhua 321000;
    2. Department of General Practice, the Second People′s Hospital of Jindong District, Jinhua City, Jinhua 321000, China
  • Received:2023-11-09 Revised:2024-01-02 Online:2024-03-05 Published:2024-02-22
  • Contact: *:yuhanqiao1990@163.com

摘要: 目的 探究髓样细胞触发受体-1(TREM-1)在慢性间歇性低氧(CIH)诱发的动脉粥样硬化(AS)中作用。方法 将ApoE-/-小鼠随机分为空白组、模型组和实验组。模型组和实验组小鼠饲养于低氧环境,给予高脂饲料喂养;实验组小鼠高脂饲养4周后,腹腔注射TREM-1抑制剂LR12(5 mg/kg),连续干预8周。饲养12周后,检测血清总胆固醇(TC)、低密度脂蛋白(LDL)、三酰甘油(TG)、肿瘤坏死因子α(TNF-α)、白细胞介素1(IL-1β)、白细胞介素10(IL-10)水平;组织学分析主动脉TREM-1表达、斑块面积及巨噬细胞水平。结果 与空白组相比,模型组小鼠主动脉TREM-1表达量显著升高(P<0.05)。相比于模型组,实验组小鼠主动脉斑块显著减少,血清血脂(TC、LDL、TG)及炎性因子(TNF-α、IL-1β、IL-10)水平显著降低,主动脉斑块及斑块浸润巨噬细胞、TREM-1表达显著减少(P<0.05),且斑块中TREM-1表达与巨噬细胞为共定位。结论 TREM-1参与CIH诱发的AS发生发展,抑制TREM-1能够减轻CIH诱发的AS,其机制与抑制巨噬细胞活化有关。

关键词: 髓样细胞触发受体-1(TREM-1), 慢性间歇性低氧, 动脉粥样硬化, 血脂, 巨噬细胞

Abstract: Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1) in atherosclerosis induced by chronic intermittent hypoxia (CIH). Methods ApoE-/- mice were randomly divided into blank group, model group and experimental group. The mice in the model group and the experimental group were kept in a hypoxic environment and fed with a high-fat diet. After 4 weeks of high-fat feeding, mice in the experimental group were intraperitoneally injected with TREM-1 inhibitor LR12 (5 mg/kg) for 8 weeks. After 12 weeks of feeding, the level of serum total cholesterol (TC), low density lipoprotein (LDL), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β) and interleukin-10 (IL-10) were detected. Histological analysis of aortic TREM-1 expression, plaque area and macrophage level were examined. Results Compared with blank group, the expression of TREM-1 in the aorta of the model group significantly increased (P<0.05). Compared with model group, the aortic plaque, the level of lipids in serum(TC, LDL, TG) and inflammatory factors (TNF-α, IL-1β, IL-10), aortic plaque, the expression of TREM-1 and infiltrating macrophages in aortic plaque of the experimental group were all significantly reduced (P<0.05). Conclusions TREM-1 is involved in the development of CIH-induced AS. Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.

Key words: triggering receptor expressed on myeloid cells-1(TREM-1), chronic intermittent hypoxia, atherosclerosis, lipids in serum, macrophage

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