增殖期糖尿病视网膜病变的血清代谢组学研究  

Plasma metabolomic profiling of proliferative diabetic retinopathy

作　　者：朱晓蓉[1,2,3] 杨芳远 卢晶 曹曦[1,2,3] 杨光燃 谢荣荣[1,2,3] 冯建萍 杨金奎[1,2,3] Zhu Xiaorong;Yang Fangyuan;Lu Jing;Cao Xi;Yang Guangran;Xie Rongrong;Feng Jianping;Yang Jinkui(Department of Endocrinology,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China;Beijing Key Laboratory of Diabetes Research and Care,Beijing 100730,China;Beijing Diabetes Institute,Beijing 100730,China)

机构地区：[1]首都医科大学附属北京同仁医院内分泌科,北京100730 [2]糖尿病防治研究北京市重点实验室,北京100730 [3]北京市糖尿病研究所,北京100730

出　　处：《首都医科大学学报》2020年第1期1-7,共7页Journal of Capital Medical University

基　　金：国家重点研发计划(2017YFC0909600);国家自然科学基金(81561128015,81471009);北京高校高精尖学科建设项目(1192070328);首都医科大学校培育基金(PYZ2018056)~~

摘　　要：目的采用代谢组学检测技术,探索增殖期糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)的“代谢图谱”及其相关的发病机制。方法从1024名2型糖尿病患者中,按照性别、年龄组间匹配的原则,选择42例患者分为PDR组和糖尿病病程10年以上且眼底完全正常(non-diabetic retinopathy,NDR)的对照组,每组各21例。应用液相色谱-质谱技术,对受试者血清代谢物进行检测,获取代谢谱。应用单维、多维统计学方法分析PDR组与NDR组之间的差异代谢物以及相关的代谢通路。结果PDR组与NDR组患者血清样本中共鉴定出136个差异代谢物质,其中包括有机酸(78%)、有机氮化合物(4%)、脂类及类脂分子(3%)等。这些代谢差异物在30条KEGG通路中富集,其中3条通路显著富集(P<0.05),分别为硫代谢、鞘脂代谢以及半胱氨酸和蛋氨酸代谢。结论PDR组与NDR组患者相比具有独特的代谢特征,硫代谢、鞘脂代谢以及半胱氨酸和蛋氨酸代谢通路显著富集。这些特征的揭示可能有助于探索新的糖尿病视网膜病变的发病机制。Objective To investigate the plasma“metabolic fingerprints”of proliferative diabetic retinopathy(PDR)and to explore associated pathogenesis.Methods A total of 1024 patients with type 2 diabetes mellitus were screened.To match clinical parameters between the case and control subjects,patients with PDR(n=21)or those with a duration of diabetes of≥10 years but non-diabetic retinopathy(NDR,n=21)were assigned to the present case-control study.Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry(LC-MS).Results A total of 136 distinct metabolites between PDR and NDR groups were identified.These metabolites mainly included organic compounds(78%),organoheterocyclic compounds(4%),lipids and lipid-like molecules(3%)and others.Altered metabolites were enriched in 30 KEGG pathways.Three of them were significantly enriched(P<0.05),namely,sulfur metabolism,sphingolipid metabolism,cysteine and methionine metabolism.Conclusion We generated a metabolomic profile for extreme eye phenotype between PDR and NDR groups.The impairment in the metabolism of sulfur,sphingolipid,cysteine and methionine were identified as metabolic dysregulation associated with PDR,which might provide insights into potential new pathogenic pathways for diabetic retinopathy.

关 键 词：2型糖尿病 增殖期糖尿病视网膜病变 代谢组学 液相色谱-质谱技术 

分 类 号：R587.2[医药卫生—内分泌]