Development of Forensic Diagnosis of Acture Sarin Poisoning

急性沙林中毒法医学诊断的进展

• 批准号: 09670431
• 负责人: NAGAO Masataka
• 金额: $ 2.37万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670431/
• 关键词: Sarin; Acethylcholinesterase; Erythocyte; Carebellum; Aikaline Phosphatase; Isopropyl methylphosphonic acid; Methylpgosphonic acid; GC-MS; Sarin; Acthyl cholinesterase; Cerebellum; Alkaline Phosphatase; methylphosphoric acid; Acthylcholineste

A sarin-like organophosphorus agent, bis (isopropyl methyl) phosphonate (BIMP), was synthesized. This agent has the same phosphonate group as sarin and also has the same anti-acethylcholinesterase activity potency as sarin. After preparation of experimental BIMP-exposed human red blood cells, BIMP-bound acetylcholinesterase (AChE) was solubilized from erythrocyte membranes, purified by immunoaffinity chromatography, digested with trypsin, and the sarin hydrolysis products bound to AChE were released by alkaline phosphatasedigestion. The digested sarin hydrolysis products were subjected to trimethylsilyl (TMS) derivatization and detected by gas chromatography-mass spectrometry (GC-MS). Isopropyl methylphosphonic and methylphosphonic acids, which are the sarin hydrolysis products, were detected in experimental BIMP-exposed human red blood cells. Using this new method, we could detected the sarin hydrolysis products from erythrocytes and formalin-fixed cerebellums of victims of the Tokyo subway terrorist attack.

合成了一种类沙林有机磷试剂--二(甲基异丙基膦)酯(BIMP)。该试剂与沙林具有相同的膦酸基，也具有与沙林相同的抗乙酰胆碱酯酶活性。制备实验性BIMP暴露的人红细胞后，从红细胞膜上溶解BIMP结合的乙酰胆碱酯酶(AChE)，免疫亲和层析纯化，胰酶消化，碱性磷酸酶消化释放与AChE结合的沙林水解物。将消化后的沙林水解物进行三甲基硅基(TMS)衍生化，用气相色谱-质谱仪(GC-MS)进行检测。在实验性BIMP暴露的人红细胞中检测到沙林的水解物异丙基甲基膦酸和甲基膦酸。使用这种新方法，我们可以检测到东京地铁恐怖袭击受害者的红细胞和福尔马林固定的小脑中的沙林水解物。

项目成果

Nagao M et al.: "Definitive evidence for the acute sarin poisoning diagnosis in the Tokyo subway." Toxicol Appl Pharmacol. 144 (1). 198-203 (1997)

Nagao M 等人：“东京地铁急性沙林中毒诊断的明确证据。”

Matsuda Y et al.: "Detrection of sarin hydrolysis product in formalin-fixed brain tissues of victims of the Tokyo Subway Terrorist Attack." Toxicol Appl Pharmacol. 150 (2). 310-20 (1998)

Matsuda Y 等人：“在东京地铁恐怖袭击受害者的福尔马林固定脑组织中检测到沙林水解产物。”

Yukimasa Matsuda et al.: "Detection of the Sarin Hydrolysis Product in the Formalin-Fixed Brain Tissue of Victims of the Tokyo Subway Terrorist Attack" Toxicology and Applied Pharmacology. 150・2. 310-320 (1998)

Yukimasa Matsuda 等：“东京地铁恐怖袭击受害者福尔马林固定脑组织中沙林水解产物的检测”毒理学和应用药理学 150・2（1998）。

Masataka Nagano et al.: "Detection of sarin hydrolysis proclucts from sarin-like organo phosphorus agent-exposed human erythrocytes" Journal of Chromatography Biomedical Applications. 701・1. 9-17 (1997)

Masataka Nagano 等人：“检测暴露于沙林样有机磷剂的人红细胞中的沙林水解产物”，色谱生物医学应用杂志 701·1（1997 年）。

Nagao M et al.: "Detrection of sarin hydrolysis products from sarin-like organo-phosphorus agent-exposed human erythrocytes." J Chromatogr B. 701 (1). 9-17 (1997)

Nagao M 等人：“从沙林样有机磷剂暴露的人红细胞中检测沙林水解产物。”