目的:通过代谢组学方法,观察大鼠尿液中的代谢物的变化,探讨偏头痛可能的发病机制。方法:实验选用SPF级Wistar大鼠20只,体重(200±20)g左右,随机分为空白组和模型组,每组10只。采用改进的Christina Tassorelli方法复制偏头痛模型,采用代谢笼法,收集大鼠造模后6 h尿液。采用超高效液相色谱和高分辨率质谱联用(UPLC-Q-TOF/MS)技术对偏头痛大鼠尿样进行代谢图谱检测。结果:与空白组的尿液相比,模型组的代谢图谱中出峰量明显增加。空白组样本和模型组样本具有一定的聚类作用,分类运动的趋势明显。从总体趋势来看,相对于空白组,模型组的代谢特征有逐渐向右运动的趋势。对模型组样本与空白组样本所得的荷载图进行分析,发现尿中5-羟吲哚乙酸、1,3-二硝酸甘油、顺乌头酸、苹果酸明显增多。结论:尿中5-羟吲哚乙酸、1,3-二硝酸甘油、顺乌头酸、苹果酸可以作为偏头痛潜在的生物标志物。
Objective: To investigate the pathogenesis of migraine in rats, with the difference of metabolites in urine of rats examined by metabonomics. Methods: A total of 20 adult Wistar rats, weighing(200±20) g, SPF grade, were randomly divided into control group and model group, with 10 rats in each group. The experimental migrainous model was duplicated by improved Christina Tassorelli Method. The urine of rats was gathered by metabolism cage 6 hours after migrainous models were duplicated. Ultraperformance liquid chromatography coupled with Q-TOF mass spectrometry(UPLC-Q-TOF/MS) was used to detect the metabolite profiles of the urine samples. Results: Compared with the control group, peaks of metabolic profiling in model group were significantly increased. Metabolite profiles of the urine sample were separated between the two groups. The model group and the control group had clustering character and the trend of classification was significant. In general, compared with the control group, metabolic profiling of the model group showed a trend of right shift. Analysis of load diagrams from rats in different groups showed that 5-HIAA, 1,3-nitroglycerin, cis-aconitic acid, and malic acid had evident increase in model group. Conclusion: 5-HIAA, 1,3-nitroglycerin, cis-aconitic acid, and malic acid in the urine samples may serve as the potential biomarkers of migraine.