Research on antemortem condition elucidation of methamphetamine detected forensic autopsy cases : investigation of trouble of skeletal muscle and kidney

法医尸检检出冰毒案件生前状况解析研究：骨骼肌及肾脏病变调查

• 批准号: 15390215
• 负责人: KUBO Shin-ichi
• 金额: $ 3.58万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390215/
• 关键词: methamphetamine; cause of death; renal function; skeletal muscle damage; myoglobin; oxidative damage; peroxidative DNA injury; immunohistochemistry; 腎機能障害; 酸化的DNA 傷害; 8-OH-dG; 尿細管傷害; CPK; 骨格筋; 腎臓; HSP70; c-Fos

In 2003, we had an immunhistochemical study on the kidney of 22 forensic autopsy cases in which methamphetamine (MA) had been detected. Myoglobin was positive in 72.7% of them. It was suspected that MA had damaged skeletal muscle. Eighty percent of HSP70-positive cases were myoglobin-positive. Myoglobin was also observed in 60.0% of 8-OH-dG-positive, in 88.6% of 4-HNE-positive, and in 77.8% of SOD-positive cases, respectively. Therefore, it was suspected that myoglobin induced oxidative injury. The relation between immunoreactivity of these substances and the concentration of MA was not found statistically. This study suggests that immunhistochemical staining of myoglobin, HSP70, 8-OH-dG, 4-HNE, and SOD contributes to presumption of the condition (just) before MA abuser's death. In 2004, we investigated the influence of MA to the kidney in rats. The single administration (group I) and the repeated administration (group II) were designed as the acute model, and the subacute or chronic model. Immunohistochemically several cell damage markers were observed. Then, the renal function markers and minerals in blood were measured. Myoglobin and creatinine phosphokinase (CPK) in blood were also analyzed. In group I, ubiquitin immunoreactivity was enhanced only in the renal tubules. Creatinine rose, and K, Ca, and P had decreased (p<0.01). CPK increased significantly (p<0.01). So, it was suspected that MA might induce the renal dysfunction with some damage in renal tubules. This damage might be related to the leakage of CPK from muscle into the blood. In group II, number of 8-OH-dG positive nucleus was increased in kidney, and quantitatively 8-OH-dG was also increased (p<0.01). It was considered that the oxidative DNA damage in the kidney might be induced by repeat administration. Blood Ca has decreased significantly (p<0.01). It was suspected that some renal dysfunction was occurred in relation to the oxidative DNA damage.

2003年，我们对22例法医尸检病例的肾脏进行了免疫组织化学研究，其中检出了甲基苯丙胺（MA）。其中 72.7% 的肌红蛋白呈阳性。人们怀疑MA损伤了骨骼肌。百分之八十的 HSP70 阳性病例是肌红蛋白阳性。肌红蛋白也分别在 60.0% 的 8-OH-dG 阳性、88.6% 的 4-HNE 阳性和 77.8% 的 SOD 阳性病例中观察到。因此，怀疑肌红蛋白诱发氧化损伤。这些物质的免疫反应性与MA浓度之间的关系在统计学上没有发现。这项研究表明，肌红蛋白、HSP70、8-OH-dG、4-HNE 和 SOD 的免疫组织化学染色有助于推测 MA 滥用者死亡前的病情。 2004年，我们研究了MA对大鼠肾脏的影响。单次给药（I组）和重复给药（II组）设计为急性模型，亚急性或慢性模型。免疫组织化学观察到多种细胞损伤标记物。然后，测量血液中的肾功能标志物和矿物质。还分析了血液中的肌红蛋白和肌酸酐磷酸激酶（CPK）。在第一组中，泛素免疫反应性仅在肾小管中增强。肌酐上升，而 K、Ca 和 P 下降 (p<0.01)。 CPK 显着增加（p<0.01）。因此，人们怀疑MA可能会诱发肾功能障碍，对肾小管造成一定的损害。这种损害可能与 CPK 从肌肉渗漏到血液中有关。在II组中，肾脏中8-OH-dG阳性核的数量增加，并且8-OH-dG的数量也增加(p<0.01)。据认为，重复给药可能会诱导肾脏中的氧化DNA损伤。血钙显着下降（p<0.01）。怀疑某些肾功能障碍的发生与 DNA 氧化损伤有关。