南方医科大学学报2018，Vol.38Issue(2)：162-167,6.DOI:10.3969/j.issn.1673-4254.2018.02.07
苯并[a]芘暴露大鼠的皮层代谢组学研究
Changes of cerebral cortical metabolomics in rats following benzo[a]pyrene exposure
摘要
Abstract
Objective To analyze the changes in endogenous small molecule metabolites after benzo[a]pyrene (B[a]P) exposure in rat cerebral cortex and explore the mechanism of B[a]P neurotoxicity. Methods Five-day-old SD rats were subjected to gavage administration of 2 mg/kg B[a]P for 7 consecutive weeks. After the exposure, the rats were assessed for spatial learning ability using Morris water maze test, ultrastructural changes of the cortical neurons under electron microscope, and metabolite profiles of the cortex using GC/MS. The differential metabolites between the exposed and control rats were identified with partial least squares discriminant analysis (PLS-DA) and the metabolic pathways related with the differential metabolites were analyzed using Cytoscape software. Results Compared with the control group, the rats exposed to B[a]P showed significantly increased escape latency (P<0.05) and decreased time spent in the target area (P<0.05). The exposed rats exhibited widened synaptic cleft, thickened endplate membrane and swollen cytoplasm compared with the control rats. Eighteen differential metabolites (VIP>1, P<0.05) in the cortex were identified between the two groups, and 9 pathways associated with B[a]P neurotoxicity were identified involving amino acid metabolism, tricarboxylic acid cycle and Vitamin B3 (niacin and nicotinamide) metabolism. Conclusion B[a]P can cause disturbance in normal metabolisms and its neurotoxicity is possibly related with disorders in amino acid metabolism, tricarboxylic acid cycle and vitamin metabolism.关键词
B[a]P/皮层/代谢组学/神经毒性Key words
benzo[a]pyrene/cortex/metabolomics/neurotoxicity引用本文复制引用
王晶,涂白杰,李春林,白璐璐,唐强虎,张瑞源,Ting-LiHan,郭玉明,Philip N.Baker,夏茵茵..苯并[a]芘暴露大鼠的皮层代谢组学研究[J].南方医科大学学报,2018,38(2):162-167,6.基金项目
国家自然科学基金(81502777,81372957) （81502777,81372957）
重庆市科委自然科学基金(2015jcyjA10032) （2015jcyjA10032）
高等学校学科创新引智计划资助(渝外专〔2016〕32号) Supported by National Natural Science Foundation of China (81502777, 81372957). （渝外专〔2016〕32号）
