论文部分内容阅读
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。
Objective To observe the effects of chronic arsenic exposure on cortical and serum metabolomics in mice and explore its neurotoxicity mechanism. Methods Twelve C57BL / 6J three-week-old male rats were randomly divided into two groups according to their body weight. The exposed group received 12 mg of sodium arsenite solution containing 50 mg / L of sodium arsenite and the control group received distilled water. After exposure, the content of arsenic in brain was determined by hydride generation-atomic fluorescence spectrometry. The metabolites of arsenic exposed group and control group were analyzed by gas chromatography / mass spectrometry (GC / MS) PCA analysis was used to compare the differences of metabolites between the two groups. The two samples were screened for difference metabolites between the two groups by t-test, and the metabolic pathways were analyzed by on-line analysis tools of metabolic pathway. Results The content of arsenic in arsenic exposure group was higher than that in control group (P <0.05). The content of phenylalanine, tyrosine, histidine, lysine and citric acid in arsenic exposure group increased High, serine, glycine, proline, aspartic acid and glutamic acid content increased, while α-ketoglutarate decreased. PCA analysis showed that the metabolic characteristics of cortex and serum in exposed group and control group were different, the difference was statistically significant (P <0.05). Conclusion Chronic arsenic exposure may affect central nervous system function by interfering with cortical and serum amino acid metabolism and tricarboxylic acid cycle, leading to the disorder of neurotransmitter synthesis and interfering with energy metabolism.