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钆生物效应代谢组学研究

发布时间:2018-07-12 19:44

  本文选题:代谢组学 + 主成分分析法 ; 参考:《燕山大学》2009年硕士论文


【摘要】: 代谢组学是后基因组时代新发展起来的一门学科,它以组群指标分析为基础,以高通量检测和数据处理为手段,以信息建模与系统整合为目标,是系统生物学的重要组成部分。该学科通过对生物体内所有低分子量代谢物进行定性和定量分析,寻找代谢物与生理病理变化的关系;代谢组学中核磁共振技术(NMR)和质谱技术(MS)是应用最广泛的两种技术,在数据分析过程中,模式识别技术例如主成分分析(PCA)、聚类分析(HCA)、偏最小二乘法(PLS)和人工神经网络(ANN)等常用来进行数据的压缩和提取。 本课题用钆作为毒性材料处理大鼠,对实验组大鼠注入不同剂量的GdCl3,并用核磁共振技术分析其肝脏和肾脏组织提取物,即可找到与钆的毒性效应相关的重要的代谢物标记物。 采用三种模式识别方法(主成分分析法,系统聚类分析法和模糊c均值聚类分析法)对大鼠肝脏和肾脏中GdCl3毒性效应的标记物数据进行分析。结果表明,肝脏中GdCl3毒性的生物标记物表现为琥珀酸、乳酸、丙氨酸、甜菜碱等浓度的升高和肝糖原浓度的降低。在肾脏中肌酸、乳酸浓度的升高和谷氨酰胺、丙氨酸、磷酸胆碱、糖磷脂、甜菜碱、肌醇以及氮氧三甲胺(TMAO)的浓度的降低,即为肾脏受损的生物标记物。通过本研究可以看出代谢组学在毒理学研究中的潜在应用性和高度的可靠性。
[Abstract]:Metabonomics is a newly developed discipline in the post-genome era. It is an important component of system biology, which is based on cluster index analysis, takes high-throughput detection and data processing as a means, and aims at information modeling and system integration. The subject explores the relationship between metabolites and physiological and pathological changes by qualitative and quantitative analysis of all low molecular weight metabolites in organisms; nuclear magnetic resonance (NMR) and mass spectrometry (MS) are two of the most widely used metabolites in metabolomics. Pattern recognition techniques such as principal component analysis (PCA), clustering analysis (HCA), partial least squares (PLS) and artificial neural network (Ann) are often used to compress and extract data. In this study, gadolinium was used as a toxic material to treat rats, and different doses of GdCl _ 3 were injected into the experimental group rats. The liver and kidney tissue extracts were analyzed by nuclear magnetic resonance (NMR), and the important metabolite markers related to the toxic effect of gadolinium were found. Three kinds of pattern recognition methods (principal component analysis, systematic cluster analysis and fuzzy c-means clustering analysis) were used to analyze the marker data of GdCl _ 3 toxicity in rat liver and kidney. The results showed that the concentrations of succinic acid, lactic acid, alanine and betaine in liver were increased and the concentration of liver glycogen was decreased. The increase of creatine, lactic acid concentration and the decrease of glutamine, alanine, choline phosphate, phospholipid, betaine, inositol and trimethylamine (TMAO) in the kidney are the biomarkers of kidney damage. The potential application and high reliability of metabonomics in toxicological research can be seen from this study.
【学位授予单位】:燕山大学
【学位级别】:硕士
【学位授予年份】:2009
【分类号】:R341

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