Chen Zhe, Tu Shenghao, Hu Yonghong, Wang Yu, Xia Yukun, Jiang Yi
Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2012 Jun;32(3):438-443. doi: 10.1007/s11596-012-0076-9. Epub 2012 Jun 9.
Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.
超过一半的类风湿性关节炎（RA）患者正在接受甲氨蝶呤（MTX）治疗。尽管MTX的疗效已得到充分证实，但在个体患者中其疗效存在差异。本研究通过代谢组学分析，检测了可用于预测MTX治疗效果的代谢生物标志物。用胶原蛋白免疫大鼠以快速诱发胶原诱导的关节炎（CIA），然后用0.1mg/kg MTX治疗4周。观察CIA的临床症状和组织病理学特征以评估治疗效果。收集CIA大鼠的尿液样本，并在治疗后使用600M 氢核磁共振（1H-NMR）进行光谱分箱分析。尿液光谱被分为光谱箱，并通过Chenomx Suite软件确定了20种内源性代谢物。进行多变量分析以识别与MTX治疗相关的内源性代谢物的光谱模式。结果显示，反应性大鼠（n = 20）尿液样本的光谱聚类与无反应性大鼠（n = 11）不同。多变量分析显示，通过偏最小二乘判别分析（PLS-DA），反应性和无反应性大鼠之间的代谢谱存在差异（R2 = 0.812，Q2 = 0.604）。在靶向分析中，选择了13种内源性代谢物（尿酸、牛磺酸、组氨酸、蛋氨酸、甘氨酸等）作为预测对MTX治疗反应的潜在生物标志物。结果表明，基于1H-NMR的代谢组学分析可用于预测MTX的治疗效果，并且发现几种代谢物与MTX的治疗效果相关。
