中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (在线): 1-6.

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创伤性脊髓损伤患者血清和尿液的代谢组学分析

宋佳婷,陈建敏,王柯文,黄蓝莹,徐森明,桂裕昌,许建文   

  1. 广西医科大学第一附属医院康复医学科,广西壮族自治区南宁市  530021
  • 收稿日期:2023-06-27 接受日期:2023-07-29 出版日期:2024-01-08 发布日期:2023-10-19
  • 通讯作者: 许建文,博士,主任医师,教授,博士生导师,广西医科大学第一附属医院康复医学科,广西壮族自治区南宁市 530021
  • 作者简介:宋佳婷,女,1996年生,陕西省咸阳市人,汉族,广西医科大学在读硕士,执业医师,主要从事脊髓损伤、脑卒中疾病的诊疗及临床研究。
  • 基金资助:
    国家自然科学基金(81960417),项目负责人:许建文;广西重点研发计划项目(桂科AB20159027),项目负责人:许建文、桂裕昌;广西自然科学基金青年科学基金项目(2022GXNSFBA035545),项目负责人:桂裕昌;广西研究生教育创新计划项目(YCB2022082),项目负责人:徐森明

Metabolomics analysis of serum and urine in patients with traumatic spinal cord injury #br#
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Song Jiating, Chen Jianmin, Wang Kewen, Huang Lanying, Xu Senming, Gui Yuchang, Xu Jianwen   

  1. Department of Rehabilitation Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • Received:2023-06-27 Accepted:2023-07-29 Online:2024-01-08 Published:2023-10-19
  • Contact: Xu Jianwen, MD, Chief physician, Professor, Doctoral supervisor, Department of Rehabilitation Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • About author:Song Jiating, Master candidate, Physician, Department of Rehabilitation Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    National Natural Science Foundation of China, No. 81960417 (to XJW); Guangxi Key Research and Development Program, No. GuiKeAB20159027 (to XJW and GYC); Guangxi Natural Science Foundation for the Youth, No. 2022GXNSFBA035545 (to GYC); Innovation Project of Guangxi Graduate Education, No. YCBZ2022082 (to XSM)

摘要:


文题释义:

创伤性脊髓损伤美国脊髓损伤协会(ASIA)分级:A级为完全性损伤,骶段(S4-5)无任何运动及感觉功能保留;B级为不完全性损伤,在神经损伤平面以下,包括骶段(S4-5)存在感觉功能,但无任何运动功能;C级为不完全性损伤,在神经损伤平面以下有运动功能,保留一半以上的关键肌肌力< 3级;D级为不完全性损伤,在神经损伤平面以下有运动功能,保留至少一半的关键肌肌力≥3级;E级为正常,感觉和运动功能正常。
代谢产物:生物体内实现代谢过程的小分子有机物(分子质量< 1 000 Da),初级代谢产物直接参与细胞的正常生长、发育、繁殖;次级代谢产物不直接参与这些过程,但通常具备重要的生理、生化功能。


背景:创伤性脊髓损伤在临床上主要依赖于量表评估与影像学检查,但对于损伤程度的预后评估具有一定局限性,利用代谢组学技术进行生物标志物筛选,对于估计病变范围、损伤与恢复程度以及开发新疗法具有重要意义。

目的:使用代谢组学技术来表征创伤性脊髓损伤患者的代谢特征,探寻潜在的生物标志物及失调的代谢途径。
方法:收集20例创伤性脊髓损伤患者(观察组)和10例健康受试者(对照组)的血清和尿液样本,进行代谢物分析,然后利用多元变量统计分析进行数据处理,筛选差异代谢物。通过MetaboAnalyst软件进行代谢通路富集,应用logistic回归构建生物标志物组合模型,并分析其与美国脊髓损伤协会(ASIA)分级的关系。

结果与结论:两组受试者的血清和尿液中分别检测出160种和73种具有显著差异的代谢物。通路富集分析显示,创伤性脊髓损伤后脂质代谢出现明显的紊乱,包括鞘脂类、亚油酸、α-亚麻酸和花生四烯酸代谢以及糖基磷脂酰肌醇生物合成。识别出他索沙坦和葫芦素糖苷这组生物标志物,并且二者构成的代谢物组合在血清和尿液中的水平与ASIA分级存在相关性。由此可见,代谢组学技术为进一步理解创伤性脊髓损伤病理机制、筛选治疗靶点提供帮助。识别出的代谢生物标志物组合可能为评估创伤性脊髓损伤的严重程度提供参考。

https://orcid.org/0000-0002-8095-591X(许建文)

关键词: 创伤性脊髓损伤, 代谢组学, 生物标志物, 差异代谢物, 超高效液相色谱-四极杆飞行时间质谱

Abstract: BACKGROUND: Traumatic spinal cord injury primarily relies on scale assessment and imaging examinations in clinical practice. However, there are limitations in predicting the prognosis of the injury. Therefore, the use of metabolomics technology for biomarker screening is significant for estimating the extent of damage, injury and recovery, as well as developing new therapies.
OBJECTIVE: To characterize the metabolic features of patients with traumatic spinal cord injury using metabolomics technology and explore potential biomarkers and disrupted metabolic pathways. 
METHODS: Serum and urine samples were collected from 20 patients with traumatic spinal cord injury (observation group) and 10 healthy subjects (control group). Metabolites were analyzed and multivariate statistical analysis was then performed for data processing to screen differential metabolites. Metabolic pathway enrichment was performed using MetaboAnalyst software. Logistic regression was applied to construct a biomarker combination model, and its relationship with the American Spinal Injury Association grading was analyzed. 
RESULTS AND CONCLUSION: Significant differences in 160 and 73 metabolites were detected in the serum and urine samples of the two groups, respectively. Pathway enrichment analysis showed evident disturbances in lipid metabolism after traumatic spinal cord injury, including sphingolipid, arachidonic acid, α-linolenic acid, and arachidonic acid metabolism, as well as glycerophospholipid and inositol phosphate biosynthesis. The combination of two identified biomarkers, telmisartan and quercetin glycoside, showed a correlation with the American Spinal Injury Association grading in both serum and urine levels. Thus, metabolomics technology provides assistance in further understanding the pathological mechanisms of traumatic spinal cord injury and screening therapeutic targets. The identified metabolic biomarker combination may serve as a reference for assessing the severity of traumatic spinal cord injury.

Key words: traumatic spinal cord injury, metabolomics, biomarker, differential metabolites, ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry

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