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OACSTPCD
Inhibition of triggering receptor expressed on myeloid cells-1(TREM-1)attenuates chronic intermittent hypoxia-induced atherosclerosis in mouse models
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.
Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1)in ath-erosclerosis 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 experi-mental 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).Com-pared 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 develop-ment of CIH-induced AS.Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.
余晗俏;李超;余育斌;冯丽娜;盛晓生;叶晓霞;王林燕
金华市人民医院 心内一科,浙江 金华 321000金华市金东区第二人民医院 全科医学科,浙江 金华 321000
临床医学
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
triggering receptor expressed on myeloid cells-1(TREM-1)chronic intermittent hypoxiaatherosclerosislipids in ser-ummacrophage
《基础医学与临床》 2024 (003)
368-373 / 6
浙江省中医药科技计划项目(2022Z@075)
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