基于~1H-NMR代谢组学技术的D-半乳糖致衰老大鼠尿液代谢谱的动态变化（英文）

发布时间：2018-08-13 15:36

【摘要】：目的通过代谢组学技术研究D-半乳糖(D-Gal)致衰老大鼠尿液代谢谱的动态变化,并探究差异代谢物和行为学指标的相关性。方法大鼠连续sc给予D-Gal 100 mg·kg-110周,并分别在第0,14,28,42,56和70天收集每只实验鼠的尿液,采用代谢组学技术对实验大鼠6次尿液样本进行核磁共振(NMR)数据采集并结合多元统计进行分析。第70天开始采用Morris水迷宫检测实验大鼠的学习记忆能力。行为学实验结束后,处死并制备脑切片,HE染色观察海马病理改变。结果对第0,14,28,42,56和70天模型组和正常对照组大鼠的尿液进行主成分分析发现,造模2~4周时,两组的代谢谱无差异;造模6~8周,两组大鼠逐渐不同;造模10周时,两组完全不同。采用正交校正的偏最小二乘判别分析寻找两组之间的差异物,在第10周发现,乳酸、丙氨酸、α-酮戊二酸和胆碱等12个峰面积具有显著性差异的潜在生物标志物。将差异代谢物和穿越平台次数、潜伏期以及目标象限停留时间进行关联分析。结果表明,模型组中含量显著性升高的差异代谢物胆碱、乳酸和二甲基甘氨酸与穿越平台次数具有显著性负相关(r=-0.90,-0.50和-0.52;n=10),甲酸与目标象限停留时间呈显著性负相关(r=-0.51,n=10);胆碱和甲酸与潜伏期呈显著性正相关(r=0.72和0.53;n=10);而模型组含量显著性降低的差异代谢物肌酸和牛磺酸与穿越平台次数具有显著性正相关(r=0.89和0.71;n=10),而丙氨酸与目标象限停留时间呈显著性正相关(r=0.74;n=10);牛磺酸、丙氨酸和肌酸与潜伏期呈显著性负相关(r=-0.66,-0.50和-0.85;n=10);进一步验证了差异代谢物与行为学指标的相关性。结论D-Gal诱导的衰老大鼠尿液代谢谱变化和其学习记忆能力损伤有一定的相关性,基于1H-NMR代谢组学的尿液代谢谱变化规律,可作为D-Gal致衰老大鼠模型成功与否的评价指标之一。
[Abstract]:Objective to study the dynamic changes of urine metabolic spectrum in aging rats induced by D-galactose (D-Gal) and to explore the correlation between different metabolites and behavioral indexes. Methods SD rats were given D-Gal 100mg kg-110 for a continuous week. Urine samples of each rat were collected on day 0, 14, 28, 42, 56 and 70, respectively. Six urine samples of experimental rats were collected by (NMR) and analyzed with multivariate statistics. The learning and memory abilities of experimental rats were measured by Morris water maze on day 70. At the end of behavioral experiment, he staining was used to observe the pathological changes of hippocampus. Results the urine of rats in the model group and the normal control group were analyzed by principal component analysis on the day 0 and 70. The results showed that there was no difference in metabolic spectrum between the two groups at 4 weeks of model making, the rats of the two groups were gradually different at 68 weeks of model making, and the two groups were completely different at 10 weeks of model making. Orthogonal corrected partial least squares discriminant analysis was used to find the difference between the two groups. In the 10th week, 12 potential biomarkers with significant differences in peak areas such as lactic acid, alanine, 伪 -ketoglutaric acid and choline were found. The differential metabolites were correlated with the times of crossing the platform, the latency and the target quadrant residence time. The results showed that the content of choline in the model group was significantly higher than that in the control group. Lactic acid and dimethyl glycine were negatively correlated with the times of crossing the platform (r = -0.90), formic acid was negatively correlated with the residence time of target quadrant (r = 0.51), choline and formic acid were positively correlated with latency (r 0.72 and 0.53 n ~ (10), while in the model group, they were positively correlated with the residence time of the target quadrant (r = 0.51), while those in the model group were positively correlated with the latency (r 0.72 and 0.53 n ~ (10). Significant positive correlation was found between creatine and taurine, which were significantly decreased (r = 0.89 and 0.71 n ~ (10), while alanine was positively correlated with the target quadrant residence time (r ~ (0.74) n ~ (10), taurine, and taurine were significantly correlated with the number of times of crossing the platform (r ~ (0.89) and (0.71) n ~ (10). There was a significant negative correlation between alanine and creatine (r ~ (-0.666) -0.50 and -0.85 n ~ (10), which further verified the correlation between different metabolites and behavioral indexes. Conclusion the changes of urine metabolic spectrum induced by D-Gal are related to the impairment of learning and memory ability in aged rats. The changes of urine metabolic spectrum based on 1H-NMR metabolomics can be used as an index to evaluate the success of aging rat model induced by D-Gal.
【作者单位】：山西大学中医药现代研究中心;山西大学化学化工学院;山西大学;山西省儿童医院妇幼保健院;中国医学科学院药物研究所;Department
【基金】：The project supported by Applied Basic Research Project of Shanxi Province(201601D021164) Innovation Project of Higher Education Institutions In Shanxi Province(2016120) Construction of Science and Technology Basic Condition Platform of Shanxi Province(2014091022) and Program of Science and Technology of Shanxi Province(20140313008-14)~~
【分类号】：R-332

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