遗传性局灶节段性肾小球硬化的治疗新进展  

Novel treatment advances in genetic focal segmental glomerulosclerosis

作　　者：叶心莹 陈嘉欣 谢静远 YE Xin-ying;CHEN Jia-xin;XIE Jingyuan(Department of Nephrology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine/Institute of Nephrology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院肾脏科、上海交通大学医学院附属肾脏病研究所,上海200025

出　　处：《中国实用内科杂志》2025年第3期204-209,共6页Chinese Journal of Practical Internal Medicine

基　　金：国家自然科学基金(82370711,81870460,82120108007)。

摘　　要：局灶节段性肾小球硬化(FSGS)是一种特定的肾脏组织学损伤模式,其病理学特征为部分肾小球及其部分毛细血管袢发生病变。足细胞的损伤和丢失是FSGS进展的关键机制。遗传性FSGS通常由影响足细胞正常生理功能或肾小球基底膜结构的基因突变引起。这些致病基因主要涉及与肾小球滤过屏障功能密切相关的基因,包括足细胞细胞骨架、离子通道及蛋白质合成等过程。临床表现主要为不同程度蛋白尿、进展性肾功能衰竭,部分患者可能合并血压升高等症状。尽管病因复杂且缺乏有效的治愈方法,但随着致病基因和发病机制研究的不断深入,特别是新治疗靶点的发现为该病的有效治疗带来希望。目前,药物治疗主要集中在免疫抑制和支持治疗,以减缓病情进展,但这些方法往往不能完全阻止疾病恶化。近年来,随着基因组学和分子生物学的进步,新的治疗策略不断涌现,如抑制内质网应激、修复线粒体功能、调节离子通道等新靶点的研究。此外,基因治疗被认为是根本性的治疗途径,研究者正在积极探索通过基因编辑技术纠正致病突变,以期为患者提供更有效的治疗选择。未来,随着科学技术的进步,针对遗传性FSGS的治疗有望取得突破性进展,提供更为精准和个体化的治疗方案。Focal segmental glomerulosclerosis(FSGS)is a specific pattern of renal histological injury,which is characterized by the pathological changes in some glomeruli and some capillary loops.Podocyte injury and loss are the key mechanisms of FSGS progression.Genetic FSGS is usually caused by mutations in genes that affect normal physiological function of podocytes or glomerular basement membrane structure.These pathogenic genes mainly involve the genes closely related to glomerular filtration barrier function,including podocyte cytoskeleton,ion channels and protein synthesis.The main clinical manifestations are varying degrees of proteinuria and progressive renal failure,and some patients may also have hypertension and other symptoms.Although the etiology is complex and there is a lack of effective therapies,the deepening of the research on pathogenic genes and pathogenesis,especially the discovery of new therapeutic targets,brings hope to the effective treatment of this disease.At present,drug therapy mainly includes immunosuppression and supportive therapy to slow the progression of the disease,but these methods often cannot completely prevent the disease from worsening.In recent years,with the progress of genomics and molecular biology,new therapeutic strategies have been emerging,such as the study on new targets of inhibiting endoplasmic reticulum stress,repairing mitochondrial function,and regulating ion channels.In addition,gene therapy is considered as a fundamental treatment approach,and researchers are actively exploring gene editing technology to correct pathogenic mutations in order to provide patients with more effective treatment options.In the future,with the progress of science and technology,the treatment forgenetic FSGS is expected to make breakthroughs and provide more accurate and individualized treatment regimens.

关 键 词：遗传性局灶节段性肾小球硬化 基因突变 药物治疗 基因治疗 

分 类 号：R5[医药卫生—内科学]