盐酸氯丙嗪急性中毒致死小鼠血浆中差异代谢物的筛选

Screening of differential metabolites in plasma of mice due to lethal acute poisoning with chlorpromazine hydrochloride

目的通过对盐酸氯丙嗪急性中毒小鼠血浆内代谢物进行非靶向代谢组学分析,筛选出与盐酸氯丙嗪急性中毒致死相关的差异代谢物。方法随机选取24只ICR小鼠并将其随机分为盐水对照组、盐酸氯丙嗪试验组,每组12只。应用超高效液相色谱-高分辨质谱(ultra-high performance liquid chromatography-high resolution mass spectrometry,UPLC-HRMS)检测两组小鼠血浆样本,通过正交偏最小二乘辨别分析、t检验及差异倍数统计方法筛选出与盐酸氯丙嗪中毒致死相关的差异代谢物,并与数据库进行对比,从而找出有差别意义的代谢产物。结果血浆样本的OPLS-DA分析结果显示,两组有较大差异;共鉴定出脂肪酰基和羧酸及其衍生物等11类共29个差异代谢产物。结论基于UPLC-HRMS的代谢组学技术能够发现与盐酸氯丙嗪中毒致死相关的差异代谢物,为今后法医学盐酸氯丙嗪中毒死因判定提供参考。

Objective To analyze and screen out differential metabolites related to lethal acute poisoning with chlorpromazine hydrochloride by non-targeted metabolomics.Methods Twenty-four ICR mice were randomly selected and divided into saline control group(n=12)and chlorpromazine hydrochloride test group(n=12).Plasma samples of the two groups were detected by ultra-high performance liquid chromatography-high resolution mass spectrometry(UPLC-HRMS).The differential metabolites related to lethal acute poisoning with chlorpromazine hydrochloride between two groups were screened by orthogonal partial least squares-discriminant analysis(OPLS-DA),t-test and fold change statistical methods and compared with the database,thereby identifying statistically significant differential metabolites.Results The results of OPLS-DA analysis of plasma samples showed significant differences between the two groups.A total of 29 differential metabolites containing 11 categories such as fatty acyl groups and carboxylic acids and their derivatives were identified.Conclusion The metabolomics technology based on UPLC-HRMS can screen differential metabolites related to lethal acute poisoning with chlorpromazine hydrochloride,which may provide a reference for future forensic determination of the cause of death from chlorpromazine hydrochloride poisoning.