天然黄酮类化合物干预DKD中NLRP3靶点研究进展  

Research progress on natural flavonoids targeting the NLRP3 in DKD

作　　者：吴夏青 张宣 王亚 王巧峰 方欢乐[1] 别蓓蓓 陈玉华 WU Xiaqing;ZHANG Xuan;WANG Ya;WANG Qiaofeng;FANG Huanle;BIE Beibei;CHEN Yuhua(Medical School of Xi'an Peihua University,Xi'an 710100,China)

机构地区：[1]西安培华学院医学院,陕西西安710100

出　　处：《海南医科大学学报》2025年第7期541-551,共11页Journal of Hainan Medical University

基　　金：西安培华学院校级科研项目资助(PHKT2322);国家自然基金青年科学基金(82104375);国家自然科学基金面上项目(82072229)。

摘　　要：糖尿病肾脏疾病(diabetic kidney disease,DKD)是一种进行性慢性糖尿病微血管并发症之一,为终末期肾病的主要原因。越来越多的证据表明,肾脏炎症在DKD发病中发挥至关重要的作用,其机制与炎症介质的过度激活相关。NLR家族pyrin域蛋白3(NLR family pyrin domain containing protein 3,NLRP3)炎症小体作为一种经典的炎症小体,可在细胞内组装成NLRP3多蛋白复合体。当机体接受内、外源性病原体或损伤时,NLRP3多蛋白复合体激发体内一系列炎症反应,促进炎症因子IL-1β、IL-18等释放,进而诱导DKD发生、发展。本文主要介绍了NLRP3炎症小体在NLRP3/Caspase-1/IL-1β通路介导的肾脏固有细胞(如肾小管上皮细胞、足细胞及系膜细胞等)异常及在DKD病理生理学反应中相关机制。除此之外,还讨论了天然黄酮类化合物作为可选择性靶向作用于肾脏内NLRP3炎性小体及其信号通路分子的候选药物在减缓炎症反应、减轻DKD症状方面的应用潜力。本文可为对DKD患者的科学管理治疗提供新思路。Diabetes kidney disease(DKD)is one of the progressive microvascular complications of the diabetes,which is the main cause of end-stage renal disease.More and more evidence suggest that renal inflammation plays a crucial role in the pathogenesis of DKD,and its mechanism is related to the excessive activation of inflammatory mediators.NLR family pyrin domain containing protein 3(NLRP3)inflammasome,as a classic inflammasome,can assemble into NLRP3 multimeric complexes in cells.When the body receives internal/external pathogens or injury,the NLRP3 multimeric complexes activates a series of inflammatory responses in the body,promoting the release of inflammatory factors IL-1βand IL-18,thereby triggering the occurrence and development of DKD.This article mainly emphasizes that the role of NLRP3 inflammasome in NLRP3/caspase-1/IL-1βpathway inducing abnormalities of renal intrinsic cells(such as tubular epithelial cells,podocytes,and mesangial cells)and the related mechanisms in the pathophysiology of DKD.In addition,the potential application of natural flavonoids as candidate drugs is used to selectively target the NLRP3 inflammasome and signaling pathway molecules for reducing the inflammatory reaction and alleviating the symptoms of DKD is discussed.The article can provide new idea for the scientific management and treatment of DKD patients.

关 键 词：糖尿病肾脏疾病(DKD) 天然黄酮 炎症 NLRP3 

分 类 号：R96[医药卫生—药理学]