| 张程,罗胜成,黄新纪,等.血浆及滑膜组织联合代谢组学揭示糖尿病促进冻结肩进展的关键代谢特征.骨科,2026,17(5): 452-458, 467. |
| 血浆及滑膜组织联合代谢组学揭示糖尿病促进冻结肩进展的关键代谢特征 |
| Key metabolic features of diabetes mellitus promoting adhesive capsulitis progression revealed by integrated plasma and synovial tissue metabolomics |
| 投稿时间：2025-12-04 |
| DOI：10.3969/j.issn.1674-8573.2026.05.008 |
| 中文关键词: 冻结肩 糖尿病 代谢组学 液相色谱-串联质谱 磷脂酰肌醇-3-激酶-蛋白激酶B 嘌呤代谢 |
| 英文关键词: Frozen shoulder Diabetes mellitus Metabolomics LC-MS/MS PI3K-Akt signaling Purine metabolism |
| 基金项目:湖南省自然基金面上项目（2022JJ30342） |
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| 中文摘要: |
| 目的 探究糖尿病与非糖尿病冻结肩患者的血浆及肩关节滑膜组织代谢特征，揭示糖尿病影响冻结肩的潜在代谢分子机制。方法 收集30例经临床诊断冻结肩患者的血浆与肩关节滑膜组织样本，按是否患有糖尿病分为未患糖尿病患者（non-diabetic，ND）组和糖尿病患者（diabetes mellitus，DM）组。ND组男7例，女8例，年龄（59.7±6.8）岁（43～76岁）；DM组男5例，女10例，年龄（57.8±7.5）岁（42～77岁）。采用液相色谱-串联质谱（LC-MS/MS）建立代谢物谱，以主成分分析（PCA）与正交偏最小二乘判别分析（OPLS-DA）进行多变量分析，并根据变量投影重要性（VIP）≥1且P<0.05筛选差异代谢物。差异代谢物进一步进行京都基因与基因组百科全书（KEGG）通路富集分析和拓扑学分析以确定关键代谢通路。结果 血浆中共鉴定184种在DM组与ND组之间存在显著差异的代谢物，主要富集于γ-氨基丁酸（GABA）能突触、胆固醇代谢和D-氨基酸代谢等通路。滑膜组织中鉴定47种存在显著差异的代谢物，富集于嘌呤代谢、cGMP依赖性蛋白激酶（PKG）和磷脂酰肌醇-3-激酶-蛋白激酶B（PI3K-Akt）等通路，整体呈下调趋势。拓扑分析显示血浆中泛酸/辅酶A（CoA）生物合成和氨基酸代谢具有较高网络影响力，而滑膜组织中嘌呤/核苷酸代谢为关键节点。结论 糖尿病冻结肩患者呈现显著的系统性与局部代谢异常，其中能量、脂类、氨基酸和核苷酸代谢及其相关信号通路可能参与冻结肩的病理过程。 |
| 英文摘要: |
| Objective To explore the metabolic characteristics of plasma and synovial tissues in patients with diabetic and non-diabetic frozen shoulder, revealing the potential metabolic molecular mechanisms by which diabetes affects frozen shoulder. Methods Plasma and synovial tissue samples were collected from 30 clinically diagnosed frozen shoulder patients, divided into a non-diabetic (ND) group and a diabetes mellitus (DM) group based on diabetes status. The ND group consisted of 7 males and 8 females, aged (59.7±6.8) years (43-76 years), while the DM group included 5 males and 10 females, aged (57.8±7.5) years (42-77 years). Metabolite profiles were established using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) for multivariate analysis. Differential metabolites were screened based on variable importance in the projection (VIP) ≥1 and P<0.05. Further Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and topological analysis were conducted to identify key metabolic pathways. Results A total of 184 metabolites were identified in plasma with significant differences between the DM and ND groups, primarily enriched in pathways such as γ-aminobutyric acid (GABA) ergic synapses, cholesterol metabolism, and D-amino acid metabolism. In synovial tissues, 47 significantly different metabolites were identified, enriched in pathways like purine metabolism, cGMP-dependent protein kinase (PKG), and phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt), showing an overall downregulation trend. Topological analysis revealed that pantetheine/coenzyme A (CoA) biosynthesis and amino acid metabolism had high network influence in plasma, while purine/nucleotide metabolism was a key node in synovial tissues. Conclusion Diabetic frozen shoulder patients exhibited significant systemic and local metabolic abnormalities, with energy, lipid, amino acid, and nucleotide metabolism and their related signaling pathways potentially involved in the pathogenesis of frozen shoulder. |
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