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

含有黄素的单加氧酶广泛存在于哺乳动物的器官中，催化仲胺和叔胺(包括甲基苯丙胺和可卡因)的N-氧化以及硫醇和硫脲的S氧化。我们注意到了这种酶，并进行了酶学和免疫组织化学检测。为了评价药物代谢酶的稳定性，研究了大鼠身体自溶肝脏中FMO活性的死后变化。以他巴唑和三甲胺为底物测定FMO的活性。FMO的MEM和TMA活性均逐渐被激活，并在死后6h达到最大活性。在那之后，酶的活性也同样迅速地下降。在法医尸检案例中，研究了FMO活性在人脑中的分布。FMO的MEM活性具有明显的区域性差异，大脑皮层活性最高，其次是丘脑、小脑、纹状体、大脑延髓、脑桥和延髓。用猪肝FMO抗体对人肝切片进行免疫组织化学检查，发现FMO在人肝腺泡内分布不均匀，所有肝细胞均呈FMO阳性，强度最高的是第3区。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曲小管和远曲小管，而不是肾小球。这些观察结果可能有助于更好地理解特定部位药物毒性的机制。最后，对神经精神药物中毒尸检案例进行了法医毒理学探讨。

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.