基于代谢组学研究方法的中药治疗高尿酸血症整体作用机制研究

Hyperuricemia (HUA) is a chronic lifelong disease resulted from the disorder of purine metabolism, and its seriousness is increasing because of the high incidence and recurrence rate. The traditional Chinese medicine has significant efficacy for the treatment of HUA. However, it is quite difficult to study their overall anti - hyperuricemia mechanism of action due to its complex composition and multi targets. This study is to develop a new metabolomics method for studing the overall anti - hyperuricemia mechanism of action of drugs and to apply the established method to study the overall anti - hyperuricemia mechanisms of action of the typical traditional Chinese medicine. Firstly, search for the biomarkers associated with HUA by analyzing the body fluid samples of the HUA animal model. Secondly, establish a new metabolomics method for studing the overall anti - hyperuricemia mechanism of action of drugs by quantiting the potential biomarkers found by the traditional metabolomics studies. Meanwhile, the drugs commonly used in clinical treatment of HUA will be examined to validate the established method. Finally, the overall anti - hyperuricemia mechanisms of action of the from Selaginella tamariscina and Polygonum Cuspidatum are studied by the established metabolomics model. The method of this study reflects the "holistic" features of the traditional Chinese medicine. The research results are expected to provide strong technical support for studing the overall anti - hyperuricemia mechanism of action of the traditional Chinese medicine.

高尿酸血症（hyperuricemia，HUA）是一种由嘌呤代谢紊乱引起的慢性终身罹患性疾病，其高发率、复发率和危害性日趋严重。中药治疗HUA的疗效显著。然而由于中药成分复杂、作用靶点多样，因此对其治疗HUA的整体作用机制研究相当困难。本研究拟建立一种用于HUA治疗药物整体作用机制研究的代谢组学新方法，并把其用于典型中药治疗HUA的作用机制研究。首先，通过分析HUA动物模型的体液样本，寻找与HUA发病相关的生物标记物；其次，在传统代谢组学研究基础上，对发现的潜在生物标记物采用液质联用技术对其进行定量，给出量化指标，同时采用临床常用治疗药物进行方法学验证，发展一种用于HUA治疗药物整体作用机制研究的代谢组学新方法。最后，应用建立的代谢组学模型研究卷柏、 虎杖治疗HUA的整体作用机制。本研究方法体现了中药作用"整体性"的特点，研究结果有望对中药治疗HUA整体作用机制的研究提供强有力的技术支撑。

高尿酸血症（hyperuricemia，HUA）是一种由嘌呤代谢紊乱引起的慢性终身罹患性疾病，其高发率、复发率和危害性日趋严重。中药治疗HUA的疗效显著。然而由于中药成分复杂、作用靶点多样，因此对其治疗HUA的整体作用机制研究相当困难。. 本项目采用基于超高效液相色谱-四级杆-飞行时间质谱仪（UPLC-Q-TOF/MS）联用技术的代谢组学方法研究中药治疗高尿酸血症大鼠的作用机制。运用主成分分析（PCA）、偏最小二乘法-判别分析（PLS-DA）和正交偏最小二乘法-判别分析（OPLS-DA）的方法对正常大鼠、高尿酸血症模型大鼠和给药组大鼠尿中的内源性代谢物进行分析，寻找并鉴定了与中药治疗高尿酸血症相关的潜在生物标记物。. 采用超高效液相色谱-三级四极杆质谱仪（UPLC-TQ-MS）联用法定量健康组、模型组和给药组大鼠尿液中13个主要潜在生物标记物包括黄尿酸、犬尿酸、吲哚-3-羧酸、肌酐、胞嘧啶、马尿酸、尿苷、硫酸吲哚酚、辛二酸、癸二酸、尿囊素、3-羟基-2-氨基苯甲酸和尿酸。所建方法灵敏、快速、重现性好、准确度高。定量结果表明，轮廓代谢组学研究中筛选出的潜在生物标记物准确可靠；虎杖对高尿酸血症大鼠的治疗作用优于卷柏。. 本研究方法体现了中药作用“整体性”的特点，研究结果有望对中药治疗HUA整体作用机制的研究提供强有力的技术支撑。