核因子-κappa B信号通路在Behçet病中的研究现状与进展  

Research status and progress of nuclear factorκappa B signaling pathway in Behçet disease

作　　者：郑传珍 张晓敏 Zheng Chuanzhen;Zhang Xiaomin(Tianjin Key Laboratory of Retinal Functions and Diseases,Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science,Eye Institute and School of Optometry,Tianjin Medical University Eye Hospital,Tianjin 300384,China)

机构地区：[1]天津医科大学眼科医院、眼视光学院、眼科研究所、国家眼耳鼻喉疾病临床医学研究中心、天津市分中心、天津市视网膜功能与疾病重点实验室,天津300384

出　　处：《中华眼底病杂志》2023年第10期862-867,共6页Chinese Journal of Ocular Fundus Diseases

基　　金：国家自然科学基金(81671642、81870651)。

摘　　要：Behçet病(BD)是一种多系统血管炎,病情交替反复发作缓解为主要特征,涉及生殖器、口腔、眼、皮肤和关节等器官。核因子(NF)-κB信号通路在BD发展中有重要作用。蛋白学研究发现,BD患者中NF-κB通路活化标志为血浆CD40配体高表达,其通过刺激中性粒细胞释放活性氧和细胞外陷阱来促进炎症。细胞学研究发现,BD患者巨噬细胞通过NF-κB通路极化为经典活化巨噬细胞型,加剧炎症。活化NF-κB与T细胞抗凋亡蛋白表达相关,延长炎症状态。微生物学研究发现,BD患者肠道菌群减少导致肠道屏障受损,NF-κB通路参与中性粒细胞和辅助性T细胞(Th)1/Th17细胞功能调控,加剧炎症。基因学研究发现,BD患者免疫调节基因多态性,通过NF-κB通路促发炎症。BD患者NF-κB相关基因突变增加风险,A20内源性抑制剂突变导致NF-κB异常活跃,维持炎症。动物实验和体外细胞实验证实,NF-κB抑制剂减轻炎症,靶向NF-κB信号通路上游炎症因子药物在BD患者疗效良好。NF-κB信号通路在BD发展中发挥关键作用,研发NF-κB抑制剂可能成为治疗BD的新途径。未来仍需进一步研究NF-κB在BD发病机制中的详细作用及其在临床治疗中的应用前景。Behcet's Disease(BD)is a multisystem vasculitis characterized by disease alternated with recurrent episodes and remissions,involving genital,oral,ocular uvea,cutaneous,and articular manifestations.The nuclear factor(NF)-κB signaling pathway paly an important role in the BD progression.It encompasses diverse gene,protein,and cellular regulatory mechanisms operating across various levels,alongside microbiological and experimental studies involving animals and cells.At the protein research findings,activation of the NF-κB pathway in BD patients is marked by elevated plasma levels of soluble CD40 ligand,which stimulates neutrophils to release reactive oxygen species and extracellular traps,thereby promoting inflammation.At the cellular research findings,macrophages in BD patients polarize towards classically activated macrophages phenotype through the NF-κB pathway,exacerbating the inflammatory response.The activation of NF-κB is associated with increased expression of anti-apoptotic proteins in T cells,leading to prolonged inflammation.Microbiological investigations reveal that the decreased gut microbiota diversity in BD patients compromises intestinal barrier integrity.NF-κB pathway involvement in regulating neutrophil and type 1 helper T cell(Th)1/Th17 cell function worsens inflammation.Genetically,BD patients exhibit polymorphisms in immune regulatory genes,which contribute to inflammation through the NF-κB pathway.Mutations in NF-κB-associated genes elevate the risk of BD,while mutations in the endogenous inhibitor A20 lead to abnormal NF-κB activity,sustaining inflammation.Animal experiments and in vitro experiments corroborate the efficacy of NF-κB inhibitors in attenuating inflammation.Targeting upstream inflammatory factors within the NF-κB pathway yields positive outcomes in BD patients.In summary,the NF-κB signaling pathway plays a pivotal role in the development of BD.Developing NF-κB inhibitors may open new avenues for treating BD.Further research is necessary to comprehensively elucidate th

关 键 词：Behçet病 核因子-ΚB信号通路 肠道菌群 基因多态性 抑制剂 综述 

分 类 号：R593.2[医药卫生—内科学] R771.3[医药卫生—临床医学]