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首页> 外文学位 >Metabolomic Strategies for Early Diagnosis of Myasthenia Gravis and Efficacy Evaluation of Qiangji Jianli Fang.
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Metabolomic Strategies for Early Diagnosis of Myasthenia Gravis and Efficacy Evaluation of Qiangji Jianli Fang.

机译：重症肌无力的早期诊断的代谢组学策略和强积健力方的疗效评估。

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摘要

Myasthenia gravis (MG) is an acquired autoimmune disease caused by specific autoantibodies against acetylcholine receptors (AChRs) and muscle-specific kinase (MuSK) proteins at the neuromuscular junctions. The disease is characterized by weakness and fatigability of the voluntary muscles that gets worse with exertion and improves with rest. The global incidence rate of MG is about 3-30 cases per million per year. In recent years, the worldwide prevalence rate of MG is increasing as a result of increased awareness. However, current diagnostic measures and treatments are not conclusive and satisfactory for MG. In this study, a mass spectrometry-based metabolomic strategy was applied to develop a novel and reliable diagnostic measure for MG on the basis of metabolic analysis, and to explore the therapeutic effect of Qiangji Jianli Fang (QJF, a newly developed Chinese medicine formula) on MG at the metabolite level.;Total 42 MG patients (13 males and 29 females) and 16 volunteers (5 males and 11 females) were recruited at the First Affiliated Hospital of Guangzhou University of Chinese Medicine between March 2007 and March 2008. The patients took QJF once per day for 2 months. Peripheral blood from patients was collected at diagnosis and after 2-month treatment, respectively. Sera prepared from the blood samples were monitored by the liquid chromatography Fourier transform mass spectrometry (LC-FTMS). Mass spectral data were analyzed by multivariate statistical analyses, including principal component analysis (PCA), orthogonal partial least squares (OPLS), and orthogonal partial least squares discriminant analysis (OPLS-DA).;By comparing analysis with the healthy volunteers, 142 significantly changed ions from serum metabolic profile of MG patients were picked out as the potential biomarkers of MG. Among of them, 14 ions were temporarily identified. They were gamma-aminobutyric acid (GABA), pipecolic acid, ornithine, 5,8-tetradecadienoic acid, spermine, hexanoylcarnitine, N-oleoyl glycine, sphingosine-1-phosphate (S1P), bisnorcholic acid, coprocholic acid, phytosphingosine-1-P, chenodeoxycholylglycine, coenzyme Q4, and cholylglycine. The developed OPLS-DA diagnostic model based on the 142 special ions showed a high sensitivity (92.8%) and specificity (83.3%) in detecting MG. QJF showed a powerful action on MG by recovering the holistic serum metabolic profile from the disease level to the normal level. Especially, the levels of GABA, pipecolic acid, ornithine, 5,8-tetradecadienoic acid, spermine, hexanoylcarnitine, N-oleoyl glycine, S1P, bisnorcholic acid, coenzyme Q4, and cholylglycine in MG patients were regulated to a relatively normal level after QJF treatment.;My results first indicated that the LC-FTMS-based metabolomics was a useful tool in biomarkers exploration of MG, and it was potentially applicable as a new diagnostic approach for MG. Also, my results demonstrated that QJF was a good optional choice for the treatment of MG, with no reported side effects.
机译：重症肌无力（MG）是一种后天性自身免疫性疾病，由针对神经肌肉接头处的乙酰胆碱受体（AChRs）和肌肉特异性激酶（MuSK）蛋白的特异性自身抗体引起。该疾病的特征是自愿性肌肉的无力和易疲劳，随着运动而变得更糟，休息时则得到改善。 MG的全球发病率约为每年每百万3-30例。近年来，由于意识的增强，MG的全球患病率正在增加。但是，目前的诊断方法和治疗方法对于MG尚无定论和令人满意。在这项研究中，基于质谱的代谢组学策略被用于在代谢分析的基础上开发出一种新颖且可靠的MG诊断方法，并探讨强积健力方（一种新开发的中药配方）的治疗效果在2007年3月至2008年3月之间，共招募了42例MG患者（男13例，女29例）和16例志愿者（5例男11例，女）在广州中医药大学第一附属医院招募。患者每天服用QJF，持续2个月。在诊断时和治疗2个月后分别收集患者的外周血。由血液样品制备的血清通过液相色谱傅里叶变换质谱法（LC-FTMS）进行监测。通过多元统计分析对质谱数据进行分析，包括主成分分析（PCA），正交偏最小二乘（OPLS）和正交偏最小二乘判别分析（OPLS-DA）。通过与健康志愿者进行比较，可将142个显着从MG患者的血清代谢谱中选择出改变的离子作为MG的潜在生物标记。其中，暂时鉴定出14个离子。它们是γ-氨基丁酸（GABA），胡椒酸，鸟氨酸，5,8-十四碳二烯酸，亚精胺，己酰基肉碱，N-油酰基甘氨酸，鞘氨醇-1-磷酸（S1P），双降胆酸，邻苯二酚酸，植物鞘氨醇-1- P，鹅去氧胆碱甘氨酸，辅酶Q4和胆碱甘氨酸。基于142种特殊离子建立的OPLS-DA诊断模型在检测MG方面显示出高灵敏度（92.8％）和特异性（83.3％）。 QJF通过将整体血清代谢谱从疾病水平恢复到正常水平，对MG表现出强大的作用。尤其是在QJF后，MG患者的GABA，胡椒酸，鸟氨酸，5,8-十四碳二烯酸，亚精胺，己酰肉碱，N-油酰甘氨酸，S1P，双降胆酸，辅酶Q4和胆碱甘氨酸的水平被调节到相对正常的水平。我的研究结果首先表明，基于LC-FTMS的代谢组学是探索MG的生物标志物的有用工具，并且有可能作为MG的新诊断方法。而且，我的结果表明，QJF是治疗MG的很好的选择，没有副作用。

著录项

  • 作者

    Lu, Yonghai.;

  • 作者单位

    The Chinese University of Hong Kong (Hong Kong).;

  • 授予单位 The Chinese University of Hong Kong (Hong Kong).;
  • 学科 Engineering System Science.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 166 p.
  • 总页数 166
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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