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NLRP3 炎性体的生物学功能:炎症性肠病的治疗靶点。

Biological functions of NLRP3 inflammasome: A therapeutic target in inflammatory bowel disease.

机构信息

Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Center for Pharmaceutics Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, 201203, China; The Institute for Translational Nanomedicine, Shanghai East Hospital, the Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, 200092, China.

出版信息

Cytokine Growth Factor Rev. 2021 Aug;60:61-75. doi: 10.1016/j.cytogfr.2021.03.003. Epub 2021 Mar 14.

Abstract

Cases of inflammatory bowel disease (IBD), a debilitating intestinal disorder with complex pathological mechanisms, have been increasing in recent years, straining the capacity of healthcare systems. Thus, novel therapeutic targets and innovative agents must be developed. Notably, the NLRP3 inflammasome is upregulated in patients with IBD and/or in animal experimental models. As an innate immune supramolecular assembly, the NLRP3 inflammasome is persistently activated during the pathogenesis of IBD by multiple stimuli. Moreover, this protein complex regulates pro-inflammatory cytokines. Thus, targeting this multiprotein oligomer may offer a feasible way to relieve IBD symptoms and improve clinical outcomes. The mechanisms by which the NLRP3 inflammasome is activated, its role in IBD pathogenesis, and the drugs administered to target this protein complex are reviewed herein. This review establishes that the use of inflammasome-targeting drugs are effective for IBD treatment. Moreover, this review suggests that the value and potential of naturally sourced or derived medicines for IBD treatment must be recognized and appreciated.

摘要

近年来,炎症性肠病(IBD)病例不断增加,这种使人虚弱的肠道疾病具有复杂的病理机制,给医疗系统带来了压力。因此,必须开发新的治疗靶点和创新药物。值得注意的是,NLRP3 炎性体在 IBD 患者和/或动物实验模型中上调。作为先天免疫超分子组装体,NLRP3 炎性体在 IBD 的发病机制中被多种刺激持续激活。此外,该蛋白复合物调节促炎细胞因子。因此,针对这种多蛋白寡聚体可能是缓解 IBD 症状和改善临床结局的可行方法。本文综述了 NLRP3 炎性体的激活机制、在 IBD 发病机制中的作用以及针对该蛋白复合物的药物。本综述证实,使用炎性体靶向药物对 IBD 的治疗有效。此外,本综述表明,必须认识到并重视天然来源或衍生药物在 IBD 治疗中的价值和潜力。

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