不随意运动型脑性瘫痪血清代谢轮廓的特征分析

Metabolic Profile of Dyskinetic Cerebral Palsy Based on Metabonomics

目的利用代谢组学方法研究不随意运动型脑瘫患儿血清代谢的轮廓特征,分析其异常代谢通路。方法收集2014年5~8月本院门诊诊断的10例6~12岁不随意运动型脑瘫患儿（患儿组）及7名正常儿童（对照组）的血清样本,利用代谢组学方法,将所有血清样本进行核磁共振扫描,所得到的核磁图谱进行分段积分,利用偏最小二乘法模型对积分矩阵回归分析,分离对照组,计算特征化学位移段。在代谢数据库中查询小分子代谢产物,分析不随意运动型脑瘫患儿代谢轮廓扰动差别。结果在偏最小二乘法模型中,15个重要变化化学位移段被确定,其中2.04 ppm、2.12 ppm、3.00 ppm、3.24 ppm、3.76 ppm、6.50 ppm信号值有显著性差异（P〈0.05）。通过生物核磁数据库发现谷氨酸、酮戊二酸、谷氨酰胺、亮氨酸、左旋丙氨酸水平升高;而牛磺酸、延胡索酸、草酰乙酸、丙酮酸、柠檬酸、天门冬氨酸、琥珀酸、苹果酸、半胱氨酸水平下降。在代谢数据库中进一步分析发现,不随意运动型脑瘫患儿血清中牛磺酸代谢通路、谷氨酸代谢通路和能量代谢通路波动异常。结论基于代谢组学偏最小二乘法模型能成功区分不随意运动型脑瘫代谢轮廓,该实验发现异常波动的代谢产物及代谢通路可成为进一步研究的重点。

Objective To analyze the metabolic profile of children with dyskinetic cerebral palsy by metabolomics, and its abnormal metabolic pathway. Methods The serum of 10 children with dyskinetic cerebral palsy（patient group） and 7 healthy children（control group）aged 6 to 12 years were collected at clinic from May to August, 2014. The serum samples were tested by the nuclear magnetic resonance spectrometer and the spectroscopies were discriminated by partial least squares-discriminant analysis. According to the human metabolome database, the final metabolites disturbed would be figured out. Results 15 chemical shifts were defined, and 6 of them, including 2.04 ppm,2.12 ppm, 3.00 ppm, 3.24 ppm, 3.76 ppm, 6.50 ppm, were significantly different between 2 groups（P〈0.05）. The KEGG Pathway Database showed that the levels of taurine, fumarate, oxaloacete, pyruvate, citrate, aspartate, succinate, malate, cysteine decreased, and the levels of glutamate, 2-oxoglutarate, glutamine, leucine, alanine increased. The abnormal metabolism was found in taurine metabolism, glutamine metabolism and energy metabolism pathways. Conclusion Based on metabolomics, the metabolic profile of children with dyskinetic cerebral palsy was discriminated out successfully. The further research can focus on the small molecules found out.