Ⅱ型糖尿病肾病模型db/db小鼠血浆的代谢组学研究

A metabonomics approach for studying on the plasma of db/db mouse as type-Ⅱ diabetic nephropathy model

目的采用基于核磁共振的代谢组学技术研究糖尿病肾病模型db/db小鼠血浆中小分子代谢物的变化。方法用核磁共振技术检测db/db小鼠(6只)和db/m小鼠(6只)血浆中的小分子代谢物,应用模式识别技术对积分数据进行正交偏最小二乘辨别(OPLS-DA)分析及相关性分析,利用MATLAB软件做相关系数图。结果统计分析结果显示,与对照组db/m小鼠相比,试验组db/db小鼠血浆中葡萄糖和氧化三甲胺(TMAO)的含量升高,多种氨基酸含量下降。结合代谢途径分析发现,糖尿病肾病小鼠体内存在氨基酸代谢异常和能量代谢异常,肾脏受到损伤。结论本文所采用的基于核磁共振的代谢组学技术能全面客观地反映糖尿病肾病小鼠血浆中的代谢物变化,潜在的代谢标志物分析及代谢途径探讨将为临床诊断及机制研究提供新思路。

Objective To investigate the characteristics of plasma metabolites in diabetic nephropathy（DN） model db/db mice.Methods NMR-based metabonomics was applied to analyze the plasma metabolic difference between db/db mice（n = 6） and db/m mice（n = 6）.OPLS-DA and Pearson′s correlative analysis was applied to integral data,the plots of correlation coefficient was constructed in MATLAB.Results Multivariate statistical analysis showed that compared to controls,there were significant changes in plasma metabolites of db/db mice,such as the increase in glucose and TMAO and the decrease in many amino acids.With analysis of metabolic pathway,the dysfunction in amino acid metabolism and energy metabolism in db/db mice could be found,and the kidney was damaged.Conclusion Work shows that NMR-based metabonomics can be used to evaluate the metabolic changes in db/db mice.The analysis of biomarkers and metabolic pathway will provide new thread for clinical diagnosis and pathophysiological study.