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| 基于UPLC-MS骨质疏松症阴虚证临床代谢标志物筛查研究 |
| Screening study of the serum metabolite biomarkers based on UPLC-MS in osteoporosis patients with liver-kidney Yin deficiency syndrome |
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| DOI：10.3969/j.issn.1006-7108.2021.09.014 |
| 中文关键词: 代谢组学 原发性骨质疏松症 肝肾阴虚症 |
| 英文关键词:metabolomics osteoporosis liver-kidney Yin deficiency syndrome (KYIDS) |
| 基金项目:国家自然科学基金（81973878）；江苏省自然科学基金(BK20180167)；无锡市卫健委转化医学专项（ZM009）；无锡市“双百”中青年医疗卫生拔尖人才项目（BJ2020063） |
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| 中文摘要: |
| 目的 筛查“肝肾阴虚证”原发性骨质疏松症患者的血清小分子差异代谢物。方法 筛选门诊符合“肝肾阴虚”证型的患者。通过纳入排除标准，筛选出肝肾阴虚组（I组）、正常组（CK组）各30例。运用UPLC-MS技术检测两组受试者血清小分子代谢物，并进行差异分析，筛选肝肾阴虚证型的差异代谢物。结果 共鉴定出小分子代谢物6 478个。初始筛选标准为OPLS-DA模型第一主成分的VIP > 1，t检验的P < 0.05。筛选I-CK组差异代谢物418个。进一步筛选标准为：①VIP > 1；②P＜0.05；③log2(FC) > 1 或者 < ?1；④Fragment score ≠ 0。共筛选出15个肝肾阴虚证差异性代谢物（氨基酸类6个：甘氨胆酸、苯丙氨酸、亮氨酸、异亮氨酸、蛋氨酸、氨基吡唑基丙酸；生物碱类2个：茶碱，骆驼蓬总碱；胆红素类2个：胆红素、(4E，15Z)-胆红素；磷脂类1个：溶血磷脂酰乙醇胺；恶唑类1个：2-甲基-4-戊氯恶唑；酚酯类1个：二苯氧苯胺；低聚肽类1个：乳基谷胱甘肽；二萜类1个：15-O DC。结论 筛选出骨质疏松症阴虚证的潜在临床代谢标志物，可用于下一步代谢通路研究。提示代谢组学技术在探索传统中医理论本质及中医药临床研究方面，具有较为广泛的应用前景。 |
| 英文摘要: |
| Objective To explore potential serum metabolic biomarkers in osteoporosis patients with liver-kidney Yin deficiency syndrome (KYIDS). Methods A total of 60 outpatients was included. They were divided into KYIDS group (Group I) and normal group (Group CK), with 30 patients in each group. Serum metabolites were identified using UPLC/MS. Data were analyzed to identify potential metabolic biomarkers of KYIDS. Results A total of 6478 small molecule metabolites were identified. The initial screening criteria were VIP>1 for the first principal component in the OPLS-DA model and p<0.05 for t-test. Differential analysis identified 418 metabolites between Group A and Group CK. Further screening criteria were: (1) VIP>1; (2) P<0.05; (3) Log2(FC)>1 or <-1; and (4) fragment score ≠ 0. Fifteen metabolites were identified as potential biomarkers of KYIDS, including 6 amino acids (glycyrrhizic acid, phenylalanine, leucine, isoleucine, methionine, and amino pyrazolyl propionic acid), 2 alkaloids (theophylline and total alkaloids of peganum harmala), 2 bilirubins (bilirubin and 4E,15Z-bilirubin), 1 phospholipid (lysophosphatidyl ethanolamine), 1 oxazole (2-methyl-4-pentyloxazole), 1 phenol ester (diphenoxy aniline), 1 oligomeric peptide (milk glutathione), and 1 diterpenoid (15-O DC). Conclusion This study successfully screened out 15 potential metabolic biomarkers of KYIDS. Metabolomics techniques would be widely applied to reveal the essence of traditional TCM theories and have a wide range of applications in clinical studies. |
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