玻璃体腔注射抗血管内皮生长因子药物治疗视网膜分支静脉阻塞继发黄斑水肿的代谢组学分析  

Metabonomics analysis of intravitreal injection of anti-vascular endothelial growth factor drugs in the treatment of macular edema secondary to branch retinal vein occlusion

作　　者：孙一宁 杨纯[1,2] 黄颖 葛丽娜[1,2] 姜丹 林冰[1,2] SUN Yining;YANG Chun;HUANG Ying;GE Lina;JIANG Dan;LIN Bing(School of Ophthalmology&Optometry,Biomedical Engineering,Wenzhou Medical University,Wenzhou 325027,China;Fundus Medicine Department,Eye Hospital of Wenzhou Medical University,Wenzhou 325027,China;Corneal and Ocular Surface Disease Specialist,Eye Hospital of Wenzhou Medical University,Wenzhou 325027,China)

机构地区：[1]温州医科大学眼视光学院(生物医学工程学院),浙江温州325027 [2]温州医科大学附属眼视光医院眼底内科,浙江温州325027 [3]温州医科大学附属眼视光医院角膜及眼表疾病专科,浙江温州325027

出　　处：《温州医科大学学报》2023年第4期285-290,共6页Journal of Wenzhou Medical University

基　　金：国家自然科学基金项目(82000909)。

摘　　要：目的:探讨视网膜分支静脉阻塞(BRVO)继发黄斑水肿(ME)患者通过玻璃体内注射血管内皮生长因子拮抗剂(anti-VEGF)治疗后眼内代谢的变化。方法:收集2021年1月至2021年6月温州医科大学附属眼视光医院20例BRVO继发ME患者抗VEGF治疗前及治疗后1个月的房水样本,采用液相色谱/质谱(LC-MS/MS)技术进行代谢物的检测,并通过主成分分析(PCA)、差异表达分析和通路富集分析等方法对代谢物进行筛选和功能注释。结果:抗VEGF治疗1个月后,所有BRVO继发ME患者的黄斑中心厚度均显著下降,差异有统计学意义(P<0.05)。PCA和OPLS-DA分析结果显示,BRVO继发ME患者房水的代谢产物与治疗前存在显著差异。通过差异表达分析发现,与治疗前相比,治疗后患者房水中的4-Oxo-2-壬烯醛含量显著升高(P<0.05),而棕榈酰溶血磷脂酰胆碱PC(16:0)、7-烯胆(甾)烷醇和PC[20:4(8Z、11Z、14Z、17Z)/P-18:0]等代谢物的含量显著降低(P<0.05)。通路富集分析结果表明,含量降低的代谢物主要富集在甘油磷脂代谢、α-亚油酸代谢和亚麻酸代谢等通路(P<0.05)。结论:抗VEGF治疗后的BRVO继发ME患者眼内代谢发生了显著变化,脂类代谢物水平明显降低。Objective:To investigate the intraocular metabolic changes in patients with macular edema(ME)secondary to branch retinal vein occlusion(BRVO)treated with intravitreal injection of vascular endothelial growth factor antagonist(anti-VEGF).Methods:The aqueous humor samples of 20 patients with ME secondary to BRVO were collected from Eye Hospital of Wenzhou Medical University during January 2021 to June 2021,before anti-VEGF treatment and 1 month after treatment,which were analyzed by liquid chromatography/mass spectrometry(LC-MS/MS)technology to detect metabolites,and metabolites were screened and functionally annotated by principal component analysis(PCA),differential metabolite analysis and pathway enrichment analysis.Results:After 1 month of anti-VEGF treatment,the central macular thickness of all ME secondary to BRVO patients was decreased with statistically significance(P<0.05).PCA results showed that metabolites of aqueous humor in patients with ME secondary to BRVO were significantly different from those before treatment.An analysis of differential metabolites found that the content of 4-Oxo-2-nonenal in the aqueous humor of patients after treatment was significantly increased(P<0.05),while palmitoyl lysophosphatidylcholine PC(16:0),7-ene and the contents of metabolites such as chol(ster)alkanol and PC[20:4(8Z,11Z,14Z,17Z)/P-18:0]were significantly decreased(P<0.05).The pathway enrichment analysis showed that metabolites with reduced content were mainly involved in biological processes such as glycerophospholipid metabolism,α-linoleic acid metabolism and linolenic acid metabolism(P<0.05).Conclusion:ME secondary to BRVO patients showed significant changes in the intraocular metabolism after anti-VEGF treatment,with significant decrease in lipid metabolism.

关 键 词：视网膜分支静脉阻塞 黄斑水肿 代谢组学 视网膜 血管内皮生长因子拮抗剂 

分 类 号：R774.5[医药卫生—眼科]