NLRP3炎症小体在糖尿病创面愈合中的作用及中医药干预的研究进展  

Role of NLRP3 Inflammasome in Diabetic Wound Healing and Intervention of Chinese Medicine:A Review

作　　者：牛文晶 刘鹏[1,2] 郭燕玲 周鑫 许彪[1,2] 王军 NIU Wenjing;LIU Peng;GUO Yanling;ZHOU Xin;XU Biao;WANG Jun(National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine(TCM),Tianjin 300193,China;Graduate School of Tianjin Universityof TCM,Tianjin 301617,China)

机构地区：[1]天津中医药大学第一附属医院,国家中医针灸临床医学研究中心,天津300193 [2]天津中医药大学研究生院,天津301617

出　　处：《中国实验方剂学杂志》2022年第24期253-260,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81973854)。

摘　　要：糖尿病创面久不愈合已成为严重的医学问题,可导致感染、截肢,甚至危及生命,同时造成了巨大社会经济负担。炎症状态的慢性化是糖尿病创面愈合过程延长的重要原因。NOD样受体蛋白3(NLRP3)炎症小体是一种细胞内蛋白复合物,包括NLRP3、凋亡相关颗粒样蛋白(ASC)、胱天蛋白酶-1前体(pro-Caspase-1),激活后可释放促炎因子白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)参与炎症反应。NLRP3炎症小体的激活与多种炎症性疾病的进展相关,研究发现糖尿病创面微循环障碍、晚期糖基化终产物累积、氧化应激损伤、巨噬细胞长期浸润等多种因素均能对NLRP3炎症小体产生影响,从而导致创面持续的炎症状态。因此,靶向NLRP3炎症小体,减少其过度激活,抑制其过度表达,成为治疗糖尿病创面的新策略。文章从糖尿病创面病理改变与NLRP3炎症小体相关联的角度,总结了调控糖尿病创面氧化应激、中性粒细胞外诱捕网(NETs)/NLRP3炎症小体轴、诱导巨噬细胞向M2型极化、减少晚期糖基化终产物的过量产生及促进自噬等方面,降低NLRP3炎症小体过度表达以促进创面修复的相关研究,并分析了目前中药有效成分及复方抑制NLRP3炎症小体激活的可能作用机制,以期为促进糖尿病创面愈合提供新的靶点,为中医药抗炎、促愈的机制研究提供方向参考。Diabetic wounds are slow to heal,which poses a challenge to the medical field.Being vulnerable to infection,they are a major cause of amputation and even death and thus are costly.Chronic inflammation is an important culprit of the lingering diabetic wounds.NOD-like receptor protein 3(NLRP3),apoptosis associated speck-like protein(ASC),and aspartate-specific proteasezymogen procaspase-1(pro-Caspase-1),constitute an intracellular protein complex called the NLRP3 inflammasome.Activated NLRP3 inflammasome can induce the release of pro-inflammatory factors interleukin(IL)-1βand IL-18 and participate in a variety of inflammatory responses.The activation of the NLRP3 inflammasome is associated with several inflammatory diseases.It has been concluded that many factors such as microcirculation disorder of diabetic wounds,accumulation of advanced glycation end products,oxidative stress injury,and long-term infiltration of macrophages can influence NLRP3 inflammasome,which induce persistent inflammation of the wounds.Therefore,solutions to the diabetic wound,such as targeting the NLRP3 inflammasome,reducing its hyperactivation,and inhibiting its overexpression,have emerged.Based on the correlation between the pathological changes of diabetic wounds and NLRP3 inflammasome,this article summarized the research on the methods of reducing NLRP3 inflammasome expression to promote the healing of diabetic wounds,such as regulating diabetic wound oxidative stress,balancing neutrophil extracellular traps(NETs)/NLRP3inflammasome axis,inducing macrophage M2 polarization,reducing the production of advanced glycation end products,and enhancing autophagy.Moreover,the mechanisms of active constituents of Chinese medicine and compound Chinese medicine prescriptions against NLRP3 inflammasome activation were analyzed.Thereby,this paper is expected to provide new targets for diabetic wound healing and a reference for research the mechanism of Chinese medicine in anti-inflammation and promoting healing.

关 键 词：糖尿病创面 NOD样受体蛋白3(NLRP3)炎症小体 中药 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学] R2-031R285.5R33