甲基苯丙胺亚急性中毒大鼠血清和尿液代谢组学研究

Serum and urine metabonomics analysis of methamphetamine subacute poisoning rats

目的运用核磁共振研究甲基苯丙胺(MA)亚急性中毒大鼠血清和尿液代谢物变化,寻找可能的生物标志物及其代谢通路,为MA中毒及滥用的毒理机制提供思路。方法 16只SD大鼠随机分为亚急性中毒组和对照组,以腹腔注射MA建立亚急性中毒模型。运用1H-NMR结合正交偏最小二乘法-判别方法分析MA中毒大鼠与对照组的血清和尿液。结果以VIP>1和P<0.05筛选出7种差异代谢物分别为2-酮戊二酸、醋酸盐、甲胺、肌酐、丙酸、琥珀酸和甘氨酸,尿液中2-酮戊二酸、甲胺、肌酐、甘氨酸呈上升趋势且具有统计学差异(P<0.05)。与差异代谢物相关的代谢通路为天冬氨酸、丙氨酸和谷氨酸代谢和柠檬酸循环。结论 2-酮戊二酸、甲胺、肌酐、甘氨酸可作为MA亚急性中毒的潜在生物标志物,天冬氨酸、丙氨酸和谷氨酸代谢和柠檬酸循环代谢途径参与MA亚急性中毒代谢过程,为MA中毒机制及鉴定MA滥用提供新思路。

Objective To investigate the metabolic changes in serum and urine of MA subacute poisoning rats,1 H NMR was applied to identify possible biomarkers and altered metabolic pathways.For further explore the toxicological mechanism of MA poisoning and abuse to provide ideas.Methods Sixteen SD rats were randomly divided into subacute poisoning group and control group.The model of subacute poisoning was established by intraperitoneal injection of MA.The serum and urine of MA poisoned rats and controls were analyzed by NMR coupled with orthogonal partial least squares-discriminant analysis（OPLS-DA）.Results Seven different metabolites were screened by VIP〉1 and P〈0.05,which were 2-oxoglutarate,acetate,methylamine,creatinine,propionate,succinate and glycine.2-oxoglutarate,methylamine,creatinine,glycine showed an upward trend with a statistically significant difference.The metabolic pathways associated with differential metabolites Aspartate,alanine and glutamate metabolism and Citrate Cycle.Conclusion 2-oxoglutarate,methylamine,creatinine,glycine can be used as potential biomarkers of MA subacute poisoning,aspartate,alanine and glutamate metabolism and citric acid cycle metabolic pathway involved in MA subacute poisoning metabolism,the potential biomarker and altered metabolic pathway provided a new orientation for exploring the toxicological mechanism of MA poisoning and abuse.