甲卡西酮对大鼠血浆代谢谱变化研究

目的应用代谢组学技术研究腹腔注射甲卡西酮大鼠血浆代谢谱的变化,筛选出可用于甲卡西酮吸毒法医学鉴定的入体生物标志物。方法SD大鼠随机分成低剂量甲卡西酮组(腹腔注射甲卡西酮溶液3mg/kg)、中剂量甲卡西酮组(腹腔注射甲卡西酮溶液12mg/kg)和对照组(腹腔注射等量生理盐水),注射3min后收集大鼠眼眶血,应用超高效液相色谱-飞行时间质谱联用技术检测血浆中内源性小分子代谢物。利用SIMCA14.1软件进行数据模式识别,根据OPLS-DA模型中的变量权重重要性排序值(Variable Importance in Projection,VIP),筛选腹腔注射甲卡西酮大鼠血浆中潜在的差异代谢物。结果对照组和实验组大鼠的血浆代谢物水平存在明显差异,并筛选出22种差异化合物可以鉴别是否吸食甲卡西酮,主要影响咖啡因代谢、嘧啶代谢、脂肪酸代谢、甘氨酸、丝氨酸、苏氨酸代谢、丙酮酸代谢以及精氨酸生物合成,并解释了注射甲卡西酮相关的中毒症状。结论甲卡西酮可影响大鼠体内代谢物组,筛选出的差异标志物有望为甲卡西酮相关案件提供法医学依据。

Analysis of methcathinone metabolic profile in Rats plasma

Objective To study the changes of plasma metabolic profile in rats with intraperitoneal injection of methcathinone,and to screen out the entry biomarkers which can be used for forensic identification of methcathinone drug abuse.Methods Two groups of rats were injected methcathinone at 3 mg/kg and 12 mg/kg by intraperitioneally respectively.The control group received the equivalent volume of saline solution.The angular vein blood of rats was collected after injection 3 min,and endogenous small molecule metabolites in plasma were investigated by ultra-performance liquid chromatography-time-of-flight mass spectrometry(UPLC-TOF-MS).The data was processed by SIMCA14.1.Differential endogenous metabolites were screened according to the ranking value of variable importance in projection(VIP).Results A total of 22 differential endogenous metabolites significantly changed in the groups exposed to methcathinone compared with the control group,which could be potential biomarkers of acute methcathinone intoxication.Conclusion This study showed that metabonomics is a useful tool in identifying biomarkers for the forensic toxicological study of methcathinone abuse.