[1]代华,夏茵茵,Ting-Li Han,等.慢性砷暴露对小鼠脑和血清代谢组学的影响[J].南方医科大学学报,2016,(09):1192.
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慢性砷暴露对小鼠脑和血清代谢组学的影响()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2016年09期
页码:
1192
栏目:
出版日期:
2016-09-16

文章信息/Info

Title:
Effect of chronic arsenic exposure on mouse brain tissue and serum metabolomics
作者:
代华夏茵茵Ting-Li HanPhilip N. Baker唐旭张瑞源杜航蔡同建程淑群
关键词:
代谢组学砷暴露神经毒性主成分分析法
Keywords:
metabolomics arsenic exposure neurotoxicity principal component analysis
摘要:
目的观察慢性砷暴露对小鼠皮层及血清代谢组学的影响,探讨其神经毒性机制。方法将12只C57BL/6J三周龄雄鼠,按 体质量随机分为2组,暴露组饮用含50 mg/L亚砷酸钠水12周,对照组饮用蒸馏水。暴露结束后,采用氢化物发生一原子荧光 光谱法测定脑砷含量;气相色谱/质谱联用法(GC/MS)对砷暴露组和对照组小鼠皮层和血清进行代谢组学研究,运用主成分分 析法(PCA)分析比较两组代谢产物的差异,两样本t检验筛选两组间差异性代谢产物,利用代谢途径在线分析工具查找其影响 的相关代谢途径。结果砷暴露组脑砷含量高于对照组,差异具有统计学意义(P<0.05);砷暴露组大脑皮层中苯丙氨酸、酪氨 酸、组氨酸、赖氨酸和柠檬酸含量升高,血清中丝氨酸、甘氨酸、脯氨酸、天门冬氨酸及谷氨酸含量升高,而α-酮戊二酸含量下 降。PCA分析显示暴露组与对照组小鼠皮层和血清代谢特征存在差异,差异具有统计学意义(P<0.05)。结论慢性砷暴露可通 过干扰皮层和血清氨基酸类代谢和三羧酸循环,导致神经递质合成障碍以及干扰能量代谢而影响中枢神经系统功能。
Abstract:
Objective To observe the effect of chronic arsenic exposure on cerebral cortex and serum metabolics of mice and explore the mechanism of arsenic neurotoxicity. Methods Twelve 3-week-old male C57BL/6J mice were randomly assigned into exposure group and control group and exposed to sodium arsenite (50 mg/L) via drinking water and deionized water for 12 weeks, respectively. After the exposure, arsenic level in the cerebrum was determined by hydride generation-atomic fluorescence spectrometry. The metabolites in the cerebral cortex and serum were determined using gas chromatography-mass spectrometry (GC/MS) analysis. Principal component analysis (PCA) was used to analyze the difference of the metabolites between the exposure and the control groups. Online tools for analyzing metabolic pathways were used to identify the related metabolites pathways. Results Arsenic content in the brain of exposure group was significantly higher than that in the control group (P<0.05). The mice exposed to arsenic had a higher level of citric acid, phenylalanine, tyrosine, histidine and lysine in the cerebral cortex (P<0.05). Serum levels of serine, glycine, proline, aspartate and glutamate were significantly higher while α-ketoglutaric acid level was significantly lower in the exposure group than in the control group (P<0.05). PCA analysis showed a significant difference in cerebral cortex and serum metabolites between the two groups. Conclusion Chronic arsenic exposure may affect the function of the central nervous system by interfering with amino acid metabolism and tricarboxylic acid cycle, which may be one of the mechanisms of arsenic neurotoxicity.

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更新日期/Last Update: 1900-01-01