NLRP3炎症小体在IgA肾病中的作用及中药干预进展

Role of NLRP3 Inflammasome in IgA Nephropathy and Chinese Medicine Intervention:A Review

免疫球蛋白(Ig)A肾病是目前公认最常见的原发性肾小球疾病,高达20%~40%的患者在发病后20年内发展为终末期肾病。针对糖基化缺陷的IgA1免疫复合物在系膜区沉积以及随后T淋巴细胞激活引起的炎症被认为是该疾病的主要原因,先天固有免疫也参与了发病。核苷酸结合寡聚化结构域样受体蛋白3是新发现的一种模式识别受体,在多种肾脏固有细胞如肾小管上皮细胞、系膜细胞和足细胞上均有表达,受外界刺激活化后可与凋亡相关斑点样蛋白(ASC)形成NOD样受体蛋白3(NLRP3)炎症体,进一步活化胱天蛋白酶-1(Caspase-1),引起白细胞介素-18(IL-18)与白细胞介素-1β(IL-1β)的成熟与释放,参与炎症反应。越来越多证据显示,NLRP3炎症小体参与了IgA肾病的发病及进展,与足细胞、系膜细胞、肾小球内皮细胞及肾小管上皮细胞等肾脏内固有细胞的损伤密切相关。中药可通过作用于NLRP3炎症小体及相关分子,调节炎性因子及其信号通路,发挥治疗IgA肾病的作用及干预其进展。该文系统综述了NLRP3炎症小体在IgA肾病中的作用,以及中药干预IgA肾病NLRP3炎症小体的临床与实验研究进展,以期为中药干预NLRP3炎症小体这一靶点的进一步研究与应用提供参考。

IgA nephropathy is recognized as the most common primary glomerular disease,with up to 20%-40%of patients developing end-stage kidney disease within 20 years of onset.The deposition of IgA1-containing immune complexes targeting glycosylation defects in the mesangial region and the subsequent inflammation caused by T lymphocyte activation are considered as the main causes of IgA nephropathy,and innate immunity is also involved in the pathogenesis.Nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)is a newly discovered pattern recognition receptor expressed in renal intrinsic cells such as renal tubular epithelial cells,mesangial cells,and podocytes.Activated by external stimuli,NLRP3 can form NLRP3 inflammasomes with apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC).The NLRP3 inflammasome can activate cysteine aspartate-specific protease-1(Caspase-1),causing the maturation and release of interleukin-18(IL-18)and interleukin-1β(IL-1β)involved in inflammation.Increasing evidence has suggested that NLRP3 inflammasomes are involved in the pathogenesis and progression of IgA nephropathy and associated with the damage of renal intrinsic cells such as podocytes,mesangial cells,endothelial cells,and renal tubular epithelial cells.Chinese medicine can regulate inflammatory cytokines and their signaling pathways by acting on NLRP3 inflammasomes and related molecules,exerting therapeutic effects on IgA nephropathy.This article introduces the role of NLRP3 inflammasomes in IgA nephropathy and reviews the clinical and experimental research progress of Chinese medicine intervention in IgA nephropathy via NLRP3 inflammasomes,aiming to provide a reference for further research and application of Chinese medicine intervention in the NLRP3 inflammasome as a new therapeutic target.