50 Hz磁场暴露对APP/PS1双转基因小鼠大脑皮层组织代谢的影响

Effects of 50 Hz magnetic field exposure on metabolism of cerebral cortex in APP/PS1 transgenic mice

目的探究50 Hz磁场暴露对APP/PS1双转基因小鼠大脑皮层组织代谢的影响。方法将12只APP/PS1双转基因12周龄雄性小鼠随机分为对照组(C组)和50 Hz磁场暴露组(MF组),每组6只。磁场暴露组小鼠暴露在1.0 mT 50 Hz磁场中,2 h/d,持续21 d;对照组小鼠除无磁场暴露外,其余条件与磁场暴露组相同。暴露结束后按标准方法取小鼠大脑皮层组织,进行高分辨非靶代谢组学检测,包括样品代谢物提取、样品LC-MS/MS质谱分析、代谢物定性定量、数据分析等。结果50 Hz磁场暴露对APP/PS1双转基因小鼠的发育无明显影响。本次高分辨非靶代谢组学检测共鉴定出1068种代谢物。依据变异倍数分析(FC>1.5或FC<0.67倍,P<0.05),50 Hz磁场暴露后小鼠皮层组织共定性出22种差异代谢物,其中11-酮-β-乳香酸增加最明显(FC=80.68),5-氨基酮戊酸降低最明显(FC=0.34)。依据OPLS-DA(VIP>1,P<0.05),共筛选30种差异代谢物,其中VIP位居前3位的是2-油酰-1-软脂酰-sn-甘油-3-磷酸胆碱(VIP=19.76,FC=0.52)、去氢抗坏血酸(VIP=12.71,FC=0.72)、肌苷(VIP=10.64,FC=1.05)。差异代谢物层次聚类分析、相关性和KEGG通路分析显示,这些差异代谢物可能参与了16条KEGG通路,其中差异代谢物L-天冬氨酸可参与其中的13条通路、L-丙氨酸可参与其中的7条通路、乙酰胆碱可参与其中的3条通路。结论50 Hz磁场暴露可能对APP/PS1双转基因小鼠的氨基酸代谢、蛋白转运、辅酶A和氨酰tRNA生物合成、肌动蛋白细胞骨架调节、神经细胞配体-受体的相互作用等方面产生一定影响。

Objective To study the effects of 50 Hz magnetic field exposure on metabolism of cerebral cortex in APP/PS1 transgenic mice.Methods Twelve 12-week-old male APP/PS1 double transgenic mice were randomly divided into the control group(C group)and the 50 Hz magnetic field exposure group(MF group)(n=6).The mice in the MF group were exposed to 1.0 mT 50 Hz magnetic field 2 h/d for 3 weeks(21 d).The mice in the sham exposure group had the same conditions as those in the MF group,except for no magnetic field exposure.After exposure,the cerebral cortex tissues of mice were taken according to the standard method for high-resolution untargeted metabonomics tests,including sample metabolite extraction,sample LC-MS/MS mass spectrometry analysis,metabolite qualitative and quantitative analysis and data analysis.Results The growth of APP/PS1 double transgenic mice were not affected after 50 Hz magnetic field exposure.The high-resolution untargeted metabonomics showed 1068 metabolites were identified.Based on fold change analysis(FC>1.5 or FC<0.67,P<0.05),22 significant changed metabolites were identified in cerebral cortex of mice after 50 Hz magnetic field exposure,and 11-keto-beta-boswellic acid was the most increased metabolite(FC=80.68),and 5-aminolevulinic acid was the most decreased metabolite(FC=0.34).Based on the variable importance in the projection(VIP)value of each variable in the orthogonal partial least-squares discriminant analysis(OPLS-DA)model(VIP>1,P<0.05),30 identified significant changed metabolites were screened in cerebral cortex of mice after 50 Hz magnetic field exposure.And the top 3 significant changed metabolites in VIP value were 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine(VIP=19.76,FC=0.52),dehydroascorbic acid(VIP=12.71,FC=0.72)and inosine(VIP=10.64,FC=1.05).The analyses of hierarchical clustering,correlation and Kyoto Encyclopedia of Genes and Genomes(KEGG)showed that the 30 VIP significant changed metabolites may be involved in 16 KEGG pathways.L-aspartic acid,L-alanine and acetylcholine may be involved in 13,7 and 3 pathways of the 16 KEGG pathways respectively.Conclusion The amino acid metabolism,ATP-binding cassette transporters,CoA and aminoacyl-tRNA biosynthesis,regulation of actin cytoskeleton and neuroactive ligand-receptor interaction may be impacted in cerebral cortex of APP/PS1 transgenic mice by 50 Hz magnetic field exposure.