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陈 宁,隋云鹏,张 亮,曹屹东,贾 栋,魏明豪.α-核突触蛋白基因突变小鼠脑组织中内源性代谢产物的变化[J].现代生物医学进展英文版,2019,19(21):4011-4016.
α-核突触蛋白基因突变小鼠脑组织中内源性代谢产物的变化
Changes of Endogenous Metabolites in Brain Tissues of Mice with Alpha - nuclear Synaptic Protein Gene Mutation
Received:June 27, 2019  Revised:July 21, 2019
DOI:10.13241/j.cnki.pmb.2019.21.003
中文关键词: α-突触核蛋白  基因突变  帕金森  代谢组学  标志性代谢产物
英文关键词: Alpha-synuclein  gene mutant  Parkinson's disease  Metabolomics  Biologically metabolical marker
基金项目:国家自然科学基金项目( 81701251)
Author NameAffiliationE-mail
CHEN Ning Department of Neurosurgery, Beijing Tiantan Hospital,Capital Medical University, Beijing, 100050, China Q13691265596@163.com 
SUI Yun-peng Department of Neurosurgery, Beijing Tiantan Hospital,Capital Medical University, Beijing, 100050, China  
ZHANG Liang Department of Neurosurgery, Tangdu HospitalAir Force Military Medical University, Xi'an, Shaanxi, 710038, China  
CAO Yi-dong Department of Neurosurgery, Tangdu HospitalAir Force Military Medical University, Xi'an, Shaanxi, 710038, China  
JIA Dong Department of Neurosurgery, Tangdu HospitalAir Force Military Medical University, Xi'an, Shaanxi, 710038, China  
WEI Ming-hao Department of Neurosurgery, Tangdu HospitalAir Force Military Medical University, Xi'an, Shaanxi, 710038, China  
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中文摘要:
      摘要 目的:明确α-核突触蛋白与帕金森病的病理生理相关性及其临床意义。方法:采用相色谱-质谱联用(UPLC-MS)检测野生型小鼠和基因突变型小鼠脑组织中内源性代谢性产物,通过mzcloud法对小鼠脑组织中内源性代谢物质进行鉴定,将相应数据进行主成分分析(PCA)和聚类分析,分析其相关差异表达代谢物,并构建通路图和互作网络图。结果:(1)基于LC/MS 法的代谢组分析结果显示两组间差异代谢物以氨基酸类及磷脂类等为主,包括β-丙氨酰-L-组氨酸、L-精氨酸、L-组氨酸、L-亮氨酸、L-苯丙氨酸、L-缬氨酸、L-天门冬氨酸、L-丙氨酸、磷脂酰胆碱等;(2)构建的代谢通路主要涉及酮体的合成和降解、牛磺酸和亚牛磺酸代谢、丙氨酸,天冬氨酸和谷氨酸代谢、精氨酸和脯氨酸代谢、组氨酸代谢、苯丙氨酸代谢、缬氨酸,亮氨酸和异亮氨酸的生物合成、甘油磷脂代谢等,从中发现18个具有标志性的代谢成分。结论:α-核突触蛋白基因突变后,酮体的合成和降解、牛磺酸和亚牛磺酸代谢、丙氨酸,天冬氨酸和谷氨酸代谢、精氨酸和脯氨酸代谢、组氨酸代谢、苯丙氨酸代谢、缬氨酸,亮氨酸和异亮氨酸的生物合成、甘油磷脂代谢等代谢通路发生了变化,涉及β丙氨酰-L-组氨酸、L-精氨酸、L-组氨酸、L-亮氨酸、L-苯丙氨酸、L-缬氨酸、L-天门冬氨酸、L-丙氨酸、磷脂酰胆碱等的生物学标志性代谢产物变化。
英文摘要:
      ABSTRACT Objective: To clarify the pathophysiological correlation between alpha-nuclear synaptic protein and Parkinson's disease and its clinical significance. Methods: Chromatography - mass spectrometry (UPLC -ms) detection of wild type mice and endogenous metabolic product of gene mutant mice brain tissue by mzcloud endogenous metabolic substances identified in brain tissue in mice, the corresponding data of principal component analysis (PCA) and cluster analysis, analysis of the relevant differentially expressed metabolites, and construct the circuit diagram and interaction network diagram. Results: (1) the results of metabolism analysis based on LC/MS method showed that the metabolites between the two groups were mainly amino acids and phospholipids, including beta-alanyl-histidine, l-arginine, l-histidine, l-leucine, l-phenylalanine, l-valine, l-aspartic acid, l-alanine, phospholipid choline, etc.(2) build the metabolic pathways of mainly relates to the synthesis and degradation of ketone body, taurine and the metabolism of taurine, alanine, glutamic acid and aspartic acid metabolism, arginine and proline metabolism, histidine metabolism, phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, glycerol phospholipid metabolism, etc., find 18 landmark metabolic components. Conclusion: after alpha nuclear synaptic protein gene mutations, ketone body of synthesis and degradation, taurine and the metabolism of taurine, alanine, glutamic acid and aspartic acid metabolism, arginine and proline metabolism, histidine metabolism, phenylalanine metabolism, valine, leucine and isoleucine biosynthesis and glycerol phospholipid metabolism in the changes of metabolic pathways, involved in beta - propylene ammonia acyl - L - histidine, L - arginine, L - histidine, L leucine, L - phenylalanine, L - valine, L - aspartate, L - alanine, phosphatidyl choline etc. Change the biological signature of metabolites.
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