增殖期糖尿病视网膜病变的血清代谢组学研究

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。

Plasma metabolomic profiling of proliferative diabetic retinopathy

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.