Enzymological and immunohistochemical study of enzyme system which participates in the narcotic and/or psychostimulant netabolism in human brain

含黄素单加氧酶（FMO）广泛分布于哺乳动物器官中，催化仲胺和叔胺（包括甲基苯丙胺和可卡因）的n氧化和硫醇和硫脲的s氧化。我们对酶进行了酶学和免疫组织化学检测。研究了大鼠尸体自溶肝脏中FMO活性的死后变化，以评价药物代谢酶的稳定性。以甲巯咪唑（MEM: s氧化）和三甲胺（TMA: n氧化）为底物测定FMO的活性。FMO的MEM和TMA活性逐渐被激活，并在死后6 h达到最大激活。之后，酶的活性同样迅速下降。在法医解剖案例中研究了FMO在人脑中的活动分布。FMO的MEM活性表现出明显的区域差异；大脑皮层的活动最高，其次是丘脑、小脑、纹状体、大脑髓质、脑桥和延髓。使用猪肝FMO抗体对人肝脏切片进行免疫组化检查，发现FMO在人肝腺泡中分布不均匀；所有肝细胞均呈FMO染色阳性，FMO染色强度在3区最高。人肾切片的免疫细胞化学检查显示该酶定位于肾皮质的近端和远端曲小管，而不是肾小球。这些观察结果可能有助于更好地理解位点特异性药物毒性的机制。最后，对神经精神药物中毒的尸检案例进行了法医毒理学分析。

The flavin-containing monooxygenase (FMO) is widely distributed in mammalian organs and catalyzes N-oxidation of secondary and tertiary amines (including methamphetamine and cocaine) and S-oxidation of thiols and thiourea. We paid attention to the enzyme, and examined enzymologically and immunohistochemically. Postmortem changes of FMO activities in the autolyzing liver of rat cadavers were studied to assess the stability of the drug-metabolizing enzymes. The activity of FMO was measured by methimazole (MEM : for S-oxidation) and trimethylamine (TMA : for N-oxidation) as substrates. Both MEM and TMA activities of FMO were formed to be gradually activated and maximum activation occurred at 6 h postmortem. After that, the activities of the enzyme were declined similarly and rapidly. The distribution of activities of FMO in human brains were studied in forensic autopsy cases. The MEM activities of FMO showed marked regional variation ; the highest activity was observed in the brain cortex, followed by the thalamus, cerebellum, striatum, cerebral medulla, pons and medulla oblongata. Immunohistochemical examination of human liver sections using an antibody produced against pig liver FMO demonstrated that FMO was non-uniformly distributed across the human liver acinus ; all hepatocytes were stained positively for FMO, with the intensity being highest in zone 3. Immunocytochemical examination of human kidney sections demonstrated localization of the enzyme in the proximal and distal convoluted tubules of the renal cortex, but not the glomeruli. These observations may lead to bette understanding of mechanism of site-specific drug toxicity. The last, we discussed forensic toxicologically about autopsy cases of poisoning by neuropsychopharmaceuticals.