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非复杂性肺结核患者脂质代谢靶点的新型治疗评估生物标志物。

Novel therapeutic evaluation biomarkers of lipid metabolism targets in uncomplicated pulmonary tuberculosis patients.

机构信息

Institute of Cell Biology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, 310058, Hangzhou, China.

The Medical Research Center of Yue Bei People's Hospital, Shantou University Medical College, 512025, Shaoguan, China.

出版信息

Signal Transduct Target Ther. 2021 Jan 18;6(1):22. doi: 10.1038/s41392-020-00427-w.

DOI:10.1038/s41392-020-00427-w
PMID:33462176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7814055/
Abstract

Currently, the management of pulmonary tuberculosis (TB) lacks potent medications and accurate efficacy evaluation biomarkers. In view of the fact that the host lipids are the important energy source of Mycobacterium tuberculosis (Mtb), UPLC-MS/MS based on lipid metabolism was used to monitor the plasma lipid spectrum of TB patients from the initial diagnosis to cured. The analysis showed that TB patients presented aberrant metabolism of phospholipids, glycerides, and sphingolipids. Upon the treatment, the abnormal expression of Cer (d18:1/24:0), CerP (d18:1/20:3), LPE (0:0/22:0), LPA (0:0/16:0), and LPA (0:0/18:0) in TB patients were gradually normalized, indicating that the intervention of lipid metabolism could block energy metabolism and inhibit the cell wall synthesis of Mtb. Furthermore, the increase in ceramide (Cer) levels could promote autophagosome-lysosome fusion. LPA (0:0/16:0) and LPA (0:0/18:0) had a great potential in the early diagnosis (both sensitivity and specificity were 100%) and efficacy evaluation (both sensitivity and specificity were 100%) of TB, indicating that the above lipid metabolites could be used as potential biomarkers for TB.

摘要

目前，肺结核（TB）的治疗缺乏有效的药物和准确的疗效评估生物标志物。鉴于宿主脂质是结核分枝杆菌（Mtb）的重要能量来源，我们采用基于脂质代谢的 UPLC-MS/MS 来监测从初诊到治愈的 TB 患者的血浆脂质谱。分析表明，TB 患者的磷脂、甘油酯和神经鞘脂代谢异常。经过治疗，Cer（d18:1/24:0）、CerP（d18:1/20:3）、LPE（0:0/22:0）、LPA（0:0/16:0）和 LPA（0:0/18:0）在 TB 患者中的异常表达逐渐趋于正常，表明干预脂质代谢可以阻断能量代谢并抑制 Mtb 的细胞壁合成。此外，神经酰胺（Cer）水平的升高可促进自噬体-溶酶体融合。LPA（0:0/16:0）和 LPA（0:0/18:0）在 TB 的早期诊断（均具有 100%的灵敏度和特异性）和疗效评估（均具有 100%的灵敏度和特异性）中具有很大的潜力，表明上述脂质代谢物可用作 TB 的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db99/7814055/9dd6b300ac46/41392_2020_427_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db99/7814055/ed8c9a7fd385/41392_2020_427_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db99/7814055/0a54e67c2d73/41392_2020_427_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db99/7814055/8cab0881a942/41392_2020_427_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db99/7814055/9dd6b300ac46/41392_2020_427_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db99/7814055/ed8c9a7fd385/41392_2020_427_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db99/7814055/cf54bb9f8bec/41392_2020_427_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db99/7814055/993cdb48c529/41392_2020_427_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db99/7814055/0a54e67c2d73/41392_2020_427_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db99/7814055/9dd6b300ac46/41392_2020_427_Fig6_HTML.jpg

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