目的:以基于核磁共振(nMr)的代谢组学方法对WIlSOn病大鼠模型及正常对照组大鼠血清进行研究,分析血清中小分子代谢物的变化,从小分子代谢物层面上探讨WIlSOn病的内在机制,以更加清楚的认识本病。方法:22只雄性WISTAr大鼠,体重(180±20)g,随机被分为模型组(n=11)和健康对照组(n=11),采用铜负荷法制作WIlSOn病大鼠模型,以核磁共振(nMr)技术对大鼠血清进行检测。采用MESTrE-C 2.3软件及自编软件对谱图进行手动调相、基线校正和谱峰对齐。对样品进行分段积分,将积分数据归一化后构成数据矩阵,并利用PCA方法对数据矩阵进行统计分析。结果:相对于正常对照组,模型组大鼠血清甜菜碱(bETAInE)、氧化三甲胺(TAMO)、低密度脂蛋白(ldl)、极低密度脂蛋白(Vldl)、葡萄糖(gluCOSE)含量有显著降低,胆碱(CHOlInE)、胆碱磷酸(PHOSPHOrylCHOlInE)的含量有所降低,乳酸(lACTATE)、谷氨酰胺(gluTAMInE)、糖蛋白(glyCOPrOTEIn)有显著升高,肌氨酸+肌氨酸酐(CrEATInE+CrEATInInE),精氨酸(ArgInInE)有所升高。这些发生改变的代谢物可以作为Wd的小分子代谢标志物,为进一步研究Wd的内在代谢机制提供参考。Objective:Applying 1H nuclear magnetic resonance(1H-NMR)spectroscopy-based metabonomic approach to investigate the changes of small molecular metabolites in the serum from the rats of the model group of Wilson's disease contrasted with those of the control group.Exploring the pathogenesis of Wilson's disease from small molecular aspect.Methods:22 male Wistar rats[weight=(180±20)g]were divided into two groups randomly,the model group(n=11)and the control group(n=11),with the models established with excessive copper method.The serum was tested with 1H-NMR technology.The spectra were edited with MestRe-C2.3 and self-programmed software and then principal component analysis(PCA)was applied to differentiate the two groups.Results:Choline and phosphorylcholine concentrations were found to be lower and TAMO+betaine,LDL,VLDL and glucose were significantly lower in the serum of the model group.While creatinine and arginine concentrations were found to be higher and lactate,glutamine and glycoprotein were significantly higher in the model group.The small molecular metabolites above may contribute to the discrimination,and serve as references for further research on WD pathogenesis.“十一五”国家科技支撑计划分课题重大疑难疾病中医防治研究项目(2006BA104A02
