【摘要】 目的 奥氮平治疗精神病疗效显著，因此其使用率逐年升高，中毒案件时有发生。体重增加作为一种常见的副作用，对其预警可以减少奥氮平中毒的发生。本文通过比较奥氮平给药后大鼠体重不变和增加组的代谢组数据，筛选出差异代谢物，建立奥氮平致大鼠体重增加的早期诊断方法。方法 30只大鼠随机分为对照组和奥氮平给药组，分别进行生理盐水和奥氮平连续灌胃处理，首次灌胃24 h后内眦静脉取血，留取血清进行代谢组分析，通过与28 d后对照组体重比较，将给药组分为体重增加组和体重不变组，比较二者的代谢组数据，筛选出差异化合物，继而建立早期诊断模型。结果 奥氮平处理后体重增加组与不变组的差异化合物有26个，其中脂质有10个，差异化合物富集在α-亚麻酸代谢、不饱和脂肪酸的生物合成、初级胆汁酸的生物合成、类固醇激素的合成通路上。结合随机森林算法，建立了早期诊断的模型，模型的预测率为80%。结论 奥氮平给药会导致大鼠代谢组发生变化，多集中在脂质上，基于26个差异代谢物建立的模型可作为奥氮平中毒的法医学早期判定的潜在方法。更多还原

【Abstract】 Objective Olanzapine has a significant effect in the treatment of mental illness, so its use has been increasing year by year, and poisoning cases have occurred from time to time. Weight gain is a common side effect, and predicting it can be used as a warning to reduce the occurrence of olanzapine poisoning. In this paper, we screened out the differential metabolites between the olanzapine administration rats whose body weight significantly increased and no significantly changed weight., therefore established an early diagnosis model for predicting olanzapine-induced weight gain in rats. Methods Thirty rats were randomly divided into the control group and olanzapine administration group, which were given continuously gavage with gthe normal saline and olanzapine for 28 days respectively. Blood was taken from the medial canthal vein on the first day after administration, and serum was collected for metabolomics analysis. The olanzapine group was divided into weight gain group and weight unchanged group by comparing with control group. The metabolic group data of the two groups were compared and the differential compounds were screened out between the two groups, Further then an early diagnosis model was established. Results There were 26 differential compounds between the weight gain group and the weight unchanged group after olanzapine administration for 28 days, including 10 lipids, which were involved in the metabolism of α-linolenic acid, the biosynthesis of unsaturated fatty acids, the biosynthesis of primary bile acids, and the synthesis of steroid hormones. Combined with the random forest algorithm, a early diagnosis model was established and the accurate rate was 80%. Conclusion Olanzapine administration would cause changes in the metabolome of rats, mostly concentrated in lipids, and the model based on 26 differential metabolites could be a candidate method for the early forensic determination of olanzapine poisoning.更多还原