原发性闭角型青光眼房水蛋白质组学研究  

Proteome Characterization of Primary Angle-Closure Glaucoma Aqueous Humor

作　　者：张婷 李科成 李霖 宋天歌 任芝霖 付春燕 兰宇 蒋黎 Zhang Ting;Li Kecheng;Li Lin;Song Tiange;Ren Zhilin;Fu Chunyan;Lan Yu;Jiang Li(Department of Laboratory Medicine,Affiliated Hospital of University of Electronic Science and Technology of China•Sichuan Provincial People's Hospital,Chengdu 610072,China)

机构地区：[1]电子科技大学附属医院·四川省人民医院临床医学检验中心,成都610072

出　　处：《成都医学院学报》2023年第2期180-186,共7页Journal of Chengdu Medical College

摘　　要：目的 分析原发性闭角型青光眼(PACG)患者房水蛋白质组表达,探寻PACG潜在生物标志物、分子机制与治疗靶点,为临床诊疗提供思路。方法 采用病例对照回顾性研究策略,纳入2020年6—12月在电子科技大学附属医院·四川省人民医院进行手术治疗的10例PACG合并白内障患者和10例单纯白内障患者进入研究。抽取患者术中房水,基于高分辨质谱非数据依赖型采集(DIA)模式分析并鉴定PACG合并白内障组与白内障组房水中蛋白质组,比较两组间房水蛋白质组差异表达,并通过基因本体富集(GO富集)、京都基因与基因组百科全书(KEGG)富集方法进一步分析差异蛋白质的功能。结果 在PACG合并白内障组与白内障组房水样本中,共鉴定出449个蛋白质,其中53个蛋白质差异有统计学意义(P<0.05),包含49个下调蛋白质及4个上调蛋白质。GO富集结果发现,差异蛋白主要来自中间丝细胞骨架、中间丝、聚合细胞骨架纤维等部位;差异蛋白的分子功能主要集中在细胞骨架组成及结构分子活性;主要参与了细胞角化、角质细胞分化、表皮细胞分化和表皮细胞发育等生物过程。使用KEGG富集方法将差异蛋白富集到了包括补体及凝血级联、过氧化物酶体增殖物激活受体信号通路、胆固醇代谢等20条不同通路中,其中补体凝血级联是KEEG通路富集最明显的一条通路。结论 本研究在PACG患者房水中发现,角质形成细胞激活标志蛋白(KRT17/KRT6/KRT16)明显下调,提示角质细胞激活及分化能力下调,与高眼压患者的角膜变薄存在潜在关联性,而补体级联效应的激活与青光眼视神经损伤息息相关。因此,角蛋白(KRT)家族蛋白有作为评估PACG患者角膜分化更新能力的标志物的潜力,抑制补体激活是PACG的潜在治疗靶点。Objective To analyze the expression of aqueous humor proteome in patients with primary angleclosure glaucoma(PACG),and to explore the potential biomarkers,molecular mechanisms,and therapeutic targets of PACG,so as to provide ideas for its clinical diagnosis and treatment.Methods A case-control retrospective study strategy was adopted.Ten PACG patients complicated with cataract(PACG combined with cataract group)and 10 patients with cataract alone(cataract group)who underwent surgery in Affiliated Hospital of University of Electronic Science and Technology of China•Sichuan Provincial People's Hospital from June to December 2020 were included in the study.Aqueous humor was extracted from patients during surgery.The proteome of the aqueous humor was analyzed and identified based on the high-resolution mass spectrometry data independent acquisition(DIA)mode.The differential expression of aqueous humor proteome between the two groups was compared.And the functions of the differential proteins were further analyzed by gene ontology enrichment(GO enrichment)and Kyoto Encyclopedia of Genes and Genome(KEGG)enrichment methods.Results A total of 449 proteins were identified in the aqueous humor samples of PACG combined with cataract group and cataract group,among which 53 proteins were significantly differentiallyexpressed (P< 0.05),including 49 down-regulated proteins and 4 up-regulated proteins. GO enrichment results showedthat the differential proteins mainly came from intermediate filaments cytoskeleton,intermediate filaments and polymericcytoskeleton fibers. The molecular functions of differential proteins mainly focus on cytoskeleton composition and structuralmolecular activity. The differential proteins were mainly involved in biological processes such as cell keratinization,keratinocyte differentiation,epidermal cell differentiation and epidermal cell development. KEGG enrichment method wasused to enrich differential proteins into 20 different pathways,including the complement coagulation cascade,peroxisomeprolifer

关 键 词：原发性闭角型青光眼 房水 蛋白质组学 角质形成细胞激活标志蛋白 

分 类 号：R775.2[医药卫生—眼科]