代谢组学研究系统性红斑狼疮的临床生物标志物和糖皮质激素治疗作用

项目名称： 代谢组学研究系统性红斑狼疮的临床生物标志物和糖皮质激素治疗作用

项目编号： No.81202601

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 严蓓

作者单位： 卫生部北京医院

项目金额： 23万元

中文摘要： 系统性红斑狼疮（SLE）是侵犯皮肤和多脏器的一种全身性自身免疫病，其药物治疗多用糖皮质激素从大剂量逐渐减量到停药，许多患者停药后病情复发。目前，SLE确切病因迄今尚未完全明了，临床也缺乏停药的定量指标。近几年代谢组学在重大疾病诊断研究以及多靶点药物药效评价中显示了巨大的优势。我们前期建立了代谢组学测定技术，并成功区分了临床中医不同证型的患者。本课题采用相同技术，全面检测不同程度SLE患者和激素治疗不同阶段以及停药前后患者体内小分子化合物，经数据处理和模式识别后，进行代谢组学分型，分析血浆内源性化合物在各组间的差异，探索SLE的潜在生物标志物、甄别激素不同治疗模式，进而进行诊断、客观量化评估预后和整体药效作用。本课题的研究成功，将在SLE发展和激素治疗的生物学机制方面取得突破性的进展，这对研究SLE的诊断和药物治疗、对于充分理解疾病的发生发展规律、指导临床合理用药具有重要的现实意义。

中文关键词： 系统性红斑狼疮；糖皮质激素；代谢组学；血清；尿液

英文摘要： Systemic lupus erythematosus (SLE) is an autoimmune disease invading skin and multiple organs. Glucocorticoid is mainly used for the treatment of SLE, and it often starts from the large dose and gradually decreases until suspended medication，but many patients will subside once stop taking drug. Currently, the exact causes of SLE have not been fully understood and it is also lack of clinical quantitative indexes for stopping taking drug. In recently years, metabonomics has shown significant advantages in diagnosis of major diseases as well as multi-targeting drug evaluation. We have already established metabonomic measurement technique, and distinguished patients with different Traditional Chinese Medicine patterns successfully. In this subject, we will use the same method to profile endogenous metabolites of patients with SLE and glucocorticoid therapy modes. We will make metabonomic classification, analyze the difference of endogenous metabolites among different groups though data processing and pattern recognition, explore the potential biomarkers of SLE and discriminate different glucocorticoid therapy modes, and then establish diagnosis system, objective quantitative evaluation system of prognosis and overall medical effects. This project has important practical significance in the study on diagnosis of SLE

英文关键词： Systemic lupus erythematosus；Glucocorticoid；Metabolomics；Serum；Urine