NLRP3 炎症酶介导 类固醇诱导的血管损伤
Thiago Bruder-Nascimento1, Nathanne S Ferreira2, Camila Z Zanotto2
1From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.). bruderthiago@usp.br rtostes@usp.br.
阿尔多斯特通过激活NLRP3炎症体,一个关键的炎症途径,导致血管损伤. 阻断这种炎症酶可以防止阿尔多引起的血管功能障碍,这表明它是一种治疗点.
科学领域:
- 心血管生物学
- 免疫学
- 分子医学
背景情况:
- 炎症是阿尔多斯特引起的血管损伤的核心原因,但其分子触发因素尚不清楚.
- NLRP3炎症酶感知危险信号并启动无菌炎症.
研究的目的:
- 研究NLRP3炎症酶在阿尔多诱导的血管功能障碍中的作用.
- 阐明阿尔多与血管炎症的分子机制.
主要方法:
- 用阿尔多斯治疗的野生型,NLRP3淘汰,卡斯巴-1淘汰和IL-1R淘汰小鼠的血管功能和炎症的分析.
- 在体外研究中使用骨髓衍生的巨细胞,用阿尔多斯激活.
- 对人类外周血液单核细胞和高血压患者的分析.
主要成果:
- 在小鼠中,阿尔多诱导了血管损伤和血IL-1β水平的升高.
- 缺乏NLRP3,caspase-1或IL-1R的小鼠受到阿尔多斯诱导的血管损伤的保护.
- 阿尔多斯特通过NF-κB和ROS激活了巨细胞中的NLRP3炎症酶,导致IL- 1β的分泌.
- 免疫细胞中的NLRP3受阿尔多激素诱导的血管损伤.
- 在人体外周血液单核细胞和高血压患者中观察到NLRP3炎症酶活性增加.
结论:
- 通过IL-1R激活,NLRP3炎症体对阿尔多斯的危害性血管作用进行了关键调解.
- 对于具有高阿尔多水平的疾病来说,NLRP3炎症酶是潜在的治疗点.
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