增殖期糖尿病视网膜病变的血清代谢组学研究

doi:10.3969/j.issn.1006-7795.2020.01.001

首都医科大学学报 ›› 2020, Vol. 41 ›› Issue (1): 1-7.doi: 10.3969/j.issn.1006-7795.2020.01.001

• 糖尿病的临床与基础研究 • 上一篇下一篇

增殖期糖尿病视网膜病变的血清代谢组学研究

朱晓蓉^1,2,3, 杨芳远^1,2,3, 卢晶^1,2,3, 曹曦^1,2,3, 杨光燃¹, 谢荣荣^1,2,3, 冯建萍¹, 杨金奎^1,2,3

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

收稿日期:2019-12-12 出版日期:2020-02-21 发布日期:2020-02-13
通讯作者: 杨金奎 E-mail:jinkui.yang@gmail.com
基金资助:
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）。

Plasma metabolomic profiling of proliferative diabetic retinopathy

Zhu Xiaorong^1,2,3, Yang Fangyuan^1,2,3, Lu Jing^1,2,3, Cao Xi^1,2,3, Yang Guangran¹, Xie Rongrong^1,2,3, Feng Jianping¹, Yang Jinkui^1,2,3

1. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;
2. Beijing Key Laboratory of Diabetes Research and Care, Beijing 100730, China;
3. Beijing Diabetes Institute, Beijing 100730, China

Received:2019-12-12 Online:2020-02-21 Published:2020-02-13
Supported by:
This study was supported by National Key R&D Program of China (2017YFC0909600),National Natural Science Foundation of China (81561128015,81471009), Construction Project of Top Disciplines in Beijing Universities (1192070328),Basic-clinical Cooperation Program from Capital Medical University (PYZ2018056).

摘要/Abstract

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1 024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。

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

Abstract: Objective To investigate the plasma "metabolic fingerprints" of proliferative diabetic retinopathy (PDR) and to explore associated pathogenesis. Methods A total of 1 024 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.

Key words: type 2 diabetes mellitus, proliferative diabetic retinopathy, metabolomic, liquid chromatography-mass spectrometry (LC-MS)

中图分类号:

R587.2

朱晓蓉, 杨芳远, 卢晶, 曹曦, 杨光燃, 谢荣荣, 冯建萍, 杨金奎. 增殖期糖尿病视网膜病变的血清代谢组学研究[J]. 首都医科大学学报, 2020, 41(1): 1-7.

Zhu Xiaorong, Yang Fangyuan, Lu Jing, Cao Xi, Yang Guangran, Xie Rongrong, Feng Jianping, Yang Jinkui. Plasma metabolomic profiling of proliferative diabetic retinopathy[J]. Journal of Capital Medical University, 2020, 41(1): 1-7.

参考文献

[1] American Diabetes Association. Microvascular complications and foot care:standards of medical care in diabetes-2018[J]. Diabetes Care,2018,41(Suppl 1):S105-S118.
[2] Klein R, Knudtson M D, Lee K E, et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy:XXII the twenty-five-year progression of retinopathy in persons with type 1 diabetes[J]. Ophthalmology,2008,115(11):1859-1868.
[3] Xu Y, Wang L, He J, et al. Prevalence and control of diabetes in Chinese adults[J]. JAMA,2013,310(9):948-959.
[4] Chen L, Cheng C Y, Choi H, et al. Plasma metabonomic profiling of diabetic retinopathy[J]. Diabetes, 2016,65(4):1099-1108.
[5] Pirola L, Balcerczyk A, Okabe J,et al. Epigenetic phenomena linked to diabetic complications[J]. Nat Rev Endocrinol,2010,6(12):665-675.
[6] Munipally P K, Agraharm S G, Valavala V K, et al. Evaluation of indoleamine 2,3-dioxygenase expression and kynurenine pathway metabolites levels in serum samples of diabetic retinopathy patients[J]. Arch Physiol Biochem,2011,117(5):254-258.
[7] Wilkinson CP, Ferris FL, 3rd, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales[J]. Ophthalmology. 2003,110(9):1677-1682.
[8] Wishart D S, Knox C, Guo A C, et al. HMDB:a knowledgebase for the human metabolome[J]. Nucleic Acids Res, 2009,37(Database issue):D603-610.
[9] Dehdashtian E, Mehrzadi S, Yousefi B, et al. Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin; involvement of autophagy, inflammation and oxidative stress[J]. Life Sci, 2018,193:20-33.
[10] Lachin J M, Genuth S, Nathan D M. et al. Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial-revisited[J]. Diabetes,2008,57(4):995-1001.
[11] Paris L P, Johnson C H, Aguilar E, et al. Global metabolomics reveals metabolic dysregulation in ischemic retinopathy[J]. Metabolomics,2016,12:15.
[12] Barba I, Garcia-Ramirez M, Hernandez C, et al. Metabolic fingerprints of proliferative diabetic retinopathy:an 1H-NMR-based metabonomic approach using vitreous humor[J]. Invest Ophthalmol Vis Sci,2010,51(9):4416-4421.
[13] Soares M S, Oliveira P S, Debom G N, et al. Chronic administration of methionine and/or methionine sulfoxide alters oxidative stress parameters and ALA-D activity in liver and kidney of young rats[J]. Amino Acids, 2017,49(1):129-138.
[14] Cabreiro F, Picot C R, Perichon M, et al. Overexpression of methionine sulfoxide reductases A and B2 protects MOLT-4 cells against zinc-induced oxidative stress[J]. Antioxid Redox Signal, 2009,11(2):215-225.
[15] Sreekumar P G, Kannan R, Yaung J, et al. Protection from oxidative stress by methionine sulfoxide reductases in RPE cells[J]. Biochem Biophys Res Commun,2005,334(1):245-253.

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

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