奥尔波特综合征致病机制及新治疗方法的研究进展  

Research progress on pathogenesis and new therapies of Alport syndrome

作　　者：郑琦敏 顾向晨 谢静远 Zheng Qimin;Gu Xiangchen;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：《中华肾脏病杂志》2023年第9期716-721,共6页Chinese Journal of Nephrology

基　　金：国家自然科学基金重点国际(地区)合作研究项目(82120108007);国家自然科学基金(81870460, 81570598);上海科委“优秀学术带头人”(21XD1402000);上海科委科技创新行动计划(22140904000, 17441902200);上海市教委高原高峰临床医学基金(20152207)。

摘　　要：奥尔波特综合征(Alport syndrom, AS)又称眼耳肾综合征或遗传性肾炎, 是常见的遗传性疾病。AS的病因为Ⅳ型胶原(type Ⅳ collagen, COL4)α3/4/5链编码基因(COL4α3、COL4α4和COL4α5)发生致病性突变, 导致肾小球、耳蜗和眼晶状体的基底膜缺陷, 患者出现血尿、蛋白尿和肾功能减退。随着AS的重新定义, 以及高通量测序技术在临床的开展, AS的发病率可能远高于以往的认识。AS的具体致病机制不明, 研究显示, COL4突变可能通过引起肾小球基底膜成分异常、脂质沉积和能量代谢紊乱、内质网应激、炎症及纤维化等导致肾脏损伤。肾素-血管紧张素系统抑制剂是目前治疗AS的主要药物, 但治疗效果不尽如人意。新的治疗策略主要包括抑制胶原异常信号传导、减轻足细胞内质网应激、调节能量代谢、抗氧化应激、抗炎症纤维化、基因治疗和干细胞治疗等, 随着研究不断深入, 有望为AS患者带来新的治疗方法。该文综述AS的致病机制及新治疗方法的研究进展。Alport syndrome(AS),also known as"eye-ear-kidney syndrome or hereditary nephritis",is a common hereditary disorder.AS is caused by pathogenic mutations of typeⅣcollagen genes(COL4α3,COL4α4 and COL4α5),leading to defects in the basement membrane of glomeruli,cochlea,and ocular lens.Patients present with hematuria,proteinuria,and progressive renal failure.With the redefinition of AS and the clinical application of high-throughput sequencing technology,the prevalence of AS may be much higher than the previously recognized.The specific pathogenic mechanism of AS is unknown.Recent studies have showed that typeⅣcollagen gene mutation may lead to kidney injury by causing abnormal basement membrane components,lipid deposition,energy metabolism disorders,endoplasmic reticulum stress,inflammation and fibrosis.Renin-angiotensin system inhibitor is the main therapy of AS,but the effect is not satisfactory.The new therapeutic strategies mainly include inhibition of abnormal collagen signal transduction,reduction of endoplasmic reticulum stress in podocytes,regulation of energy metabolism,antioxidant stress,anti-inflammation and fibrosis,gene and stem cell therapy.The paper reviewed the research progress on pathogenesis and new therapies of AS.

关 键 词：ALPORT综合征 遗传性疾病 先天性 治疗学 致病机制 

分 类 号：R692.3[医药卫生—泌尿科学]