中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (24): 5116-5126.doi: 10.12307/2025.734

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非靶向代谢组学分析影响轻中度脑卒中后认知功能障碍的生物标记物

王之枫1，杨  娇2，郗域江1，徐双凤1，施  婷1，蓝浚峯1，郝志慧1，和鹏芬1，杨爱明3，潘  攀2，王  健1   

  1. 1云南中医药大学第一临床医学院，云南省昆明市  650000；2云南中医药大学第二附属医院，云南省昆明市  650000；3云南省中医医院，云南省昆明市  650021
  • 收稿日期:2024-08-08 接受日期:2024-10-22 出版日期:2025-08-28 发布日期:2025-01-24
  • 通讯作者: 王健，博士，副教授，云南中医药大学第一临床医学院，云南省昆明市 650000 共同通讯作者：潘攀，博士，讲师，云南中医药大学第二附属医院，云南省昆明市 650000
  • 作者简介:王之枫，男，1998年生，四川省绵阳市人，汉族，云南中医药大学第一临床医学院在读硕士，主要从事脑卒中疾病的诊疗及临床研究。
  • 基金资助:
    云南省应用基础研究计划一般项目(202201AT070214)，项目负责人：王健；云南省科技厅-中医药应用基础研究联合专项资金(202001AZ070001-020，202301AZ070001-016)，项目负责人：王健；云南省两类人才项目(202205AD160024)，项目负责人：王健；云南省教育厅科学研究基金项目(2024Y398)，项目负责人：王之枫；云南省教育厅科学研究基金项目(2024Y391)，项目负责人：和鹏芬；云南省科学技术厅-基础研究计划(202201AU070176)，项目负责人：潘攀

Biomarkers affecting the progression of mild to moderate cognitive impairment after stroke: #br# a non-targeted metabolomics analysis

Wang Zhifeng1, Yang Jiao2, Xi Yujiang1, Xu Shuangfeng1, Shi Ting1, Lan Junfeng1, Hao Zhihui1, He Pengfen1, Yang Aiming3, Pan Pan2, #br# Wang Jian1#br#   

  1. 1The First Clinical Medical College of Yunnan University of Chinese Medicine, Kunming 650000, Yunnan Province, China; 2The Second Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming 650000, Yunnan Province, China; 3Yunnan Hospital of Traditional Chinese Medicine, Kunming 650021, Yunnan Province, China
  • Received:2024-08-08 Accepted:2024-10-22 Online:2025-08-28 Published:2025-01-24
  • Contact: Wang Jian, MD, Associate professor, The First Clinical Medical College of Yunnan University of Chinese Medicine, Kunming 650000, Yunnan Province, China Co-corresponding author: Pan Pan, MD, Lecturer, The Second Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming 650000, Yunnan Province, China
  • About author:Wang Zhifeng, Master candidate, The First Clinical Medical College of Yunnan University of Chinese Medicine, Kunming 650000, Yunnan Province, China
  • Supported by:
    General Project of Applied Basic Research Program of Yunnan Province, No. 202201AT070214 (to WJ); Joint Special Funds for Applied Basic Research in Traditional Chinese Medicine of Yunnan Provincial Department of Science and Technology, Nos. 202001AZ070001-020 and 202301AZ070001-016 (to WJ); Two-type Talents Project of Yunnan Province, No. 202205AD160024 (to WJ); Scientific Research Fund Project of Yunnan Provincial Department of Education, Nos. 2024Y398 (to WZF) and 2024Y391 (to HPF); Department of Science and Technology of Yunnan Province - Basic Research Program, No. 202201AU070176 (to PP)

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摘要：


文题释义：
脑卒中后认知功能障碍：是指在脑卒中事件后出现并持续到一定时间(如6个月)仍存在的以认知损害为特征的临床综合征。
非靶向代谢组学：采用液相色谱-质谱联用技术(LC-MS)、气相色谱-质谱联用技术(GC-MS)和核磁共振(NMR)等技术，无偏向性地检测细胞、组织、器官或者生物体内受到刺激或扰动前后所有小分子代谢物(主要是分子质量1 000 Da以内的内源性小分子化合物)的动态变化。

背景：认知功能障碍是脑卒中后的常见并发症，其严重程度与患者的预后密切相关。如果能尽早识别患者的认知功能障碍严重程度并进行针对性治疗，那么患者的预后可以得到显著改善。
目的：初步探索影响脑卒中后认知功能障碍疾病进展的潜在生物标志物，为其病理生理机制研究提供更为丰富和独特的参考依据。
方法：采用高效液相色谱-质谱联用技术，对轻度与中度脑卒中后认知功能障碍患者的血清样本进行非靶向代谢组学分析，筛选出两组间差异代谢物，为了进一步验证差异代谢物的诊断效能，运用受试者工作特征曲线分析，评估它们在区分疾病严重程度方面的准确性和敏感性，此外还进行了差异代谢物通路分析。
结果与结论：①轻度与中度脑卒中后认知功能障碍患者代谢谱存在显著差异，通过受试者工作特征曲线筛选出9个差异代谢物；②差异代谢物通路分析发现，影响轻、中度脑卒中后认知功能障碍患者疾病进展的代谢途径包括色氨酸代谢、D-氨基酸代谢、生物素代谢、视黄醇代谢、氨酰-tRNA生物合成、赖氨酸降解、蛋白质的消化和吸收、嘧啶代谢、半胱氨酸和甲硫氨酸代谢、ABC转运蛋白、氨基酸的生物合成、2-氧代羧酸代谢。结果筛选出影响轻、中度脑卒中后认知功能障碍患者疾病进展的潜在生物标志物9个，涉及色氨酸代谢、D-氨基酸代谢和视黄醇代谢等12条代谢途径。
https://orcid.org/0000-0003-3080-2795(王之枫)


中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 脑卒中后认知功能障碍, 非靶向代谢组学, 超高效液相色谱-质谱联用技术, 生物标志物, 差异代谢物, 曲线下面积, 变量投影重要度

Abstract: BACKGROUND: Cognitive impairment is the most common complication after stroke, and its severity is closely related to the patient’s prognosis. The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early. 
OBJECTIVE: To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment, thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.
METHODS: Using ultra performance liquid chromatography-mass spectrometry, non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups. To further validate the diagnostic efficacy of the differential metabolites, the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity. In addition, pathway analysis was conducted on the differential metabolites.
RESULTS AND CONCLUSION: (1) There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment, and 9 differential metabolites were screened by the receiver operating characteristic curve. (2) Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism, D-amino acid metabolism, biotin metabolism, retinol metabolism, aminoacyl-tRNA biosynthesis, lysine degradation, protein digestion and uptake, pyrimidine metabolism, cysteine and methionine metabolism, ABC transporter proteins, amino acid biosynthesis, and 2-oxocarboxylic acid metabolism. To conclude, 9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified, involving 12 metabolic pathways including tryptophan metabolism, D-amino acid metabolism and retinol metabolism.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: post-stroke cognitive impairment, non-targeted metabolomics, ultra performance liquid chromatography-mass spectrometry, biomarker, differential metabolites, area under the curve, variable importance in projection

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