【摘要】 目的 通过非靶向代谢物组学，分析急性胰岛素中毒大鼠血清代谢产物的变化，寻找与急性胰岛素中毒高度相关的内源性代谢特征，为法医学鉴定急性胰岛素中毒提供辅助依据。方法 建立对照组、胰岛素低剂量组以及胰岛素高剂量组大鼠模型。运用超高效液相色谱-四极杆-静电轨道阱-高分辨质谱（UPLC-Q-Exactive-Orbitrap MS）采集血清的内源性代谢物谱，使用生物信息学方法，根据OPLS-DA模型中的变量重要性投影值（VIP）结合FC值筛选出与急性胰岛素中毒相关的特征代谢物，并对特征代谢物进行通路分析。结果 筛选出18种与胰岛素剂量无关的差异代谢物，其中4种代谢物在给药组中含量上升，14种代谢物在给药组中含量下降。这些小分子代谢物主要集中在鞘脂代谢和初级胆汁酸生物合成代谢通路中。结论 胰岛素中毒引起体内小分子代谢物的变化，结合筛选出的差异代谢物，可为胰岛素中毒的法医学判定提供辅助性依据。更多还原

【Abstract】 Objective To investigate serum metabolic alterations in rats with acute insulin poisoning using nontargeted metabolomics, and to identify endogenous metabolic features closely associated with acute insulin poisoning, thereby providing auxiliary evidence for its forensic identification. Methods Rat models were established for a control group, a low-dose insulin group, and a high-dose insulin group. Endogenous serum metabolite profiles were acquired using ultra-performance liquid chromatography coupled with quadrupole–Orbitrap high-resolution mass spectrometry(UPLCQ-Exactive-Orbitrap MS). Bioinformatics analyses were performed to screen characteristic metabolites associated with acute insulin poisoning based on variable importance in projection(VIP) values from the OPLS-DA model combined with fold change(FC) criteria. Pathway analysis was subsequently conducted for the identified metabolites. Results A total of 18 differential metabolites independent of insulin dose were identified, among which 4 metabolites were upregulated and 14 metabolites were downregulated in the insulin-treated groups. These small-molecule metabolites were mainly enriched in sphingolipid metabolism and primary bile acid biosynthesis pathways. Conclusion Acute insulin poisoning induces distinct alterations in endogenous small-molecule metabolites. The identified differential metabolites may serve as auxiliary indicators for the forensic determination of insulin poisoning.更多还原