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

2003年，我们对22例检出甲基苯丙胺(MA)的法医身体的肾脏进行了免疫组织化学研究。肌红蛋白阳性者占72.7%。怀疑MA对骨骼肌造成了损害。在HSP70阳性的病例中，80%为肌红蛋白阳性。肌红蛋白在8-OH-DG阳性、4-HNE阳性和SOD阳性病例中的阳性检出率分别为60.0%、88.6%和77.8%。因此，有可能是肌红蛋白引起了氧化损伤。这些物质的免疫反应性与MA浓度的关系未见统计学意义。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滥用者死亡前的状况。2004年，我们研究了MA对大鼠肾脏的影响。采用单次给药(I组)和多次给药(II组)作为急性模型，亚急性或慢性模型。免疫组织化学染色观察了几种细胞损伤标志物。检测肾功能指标和血中矿物质含量。同时检测血液中肌红蛋白和肌酸磷酸激酶(CPK)的含量。在I组，泛素免疫反应仅在肾小管中增强。肌酐升高，K、Ca、P降低(p&lt；0.01)。CPK显著升高(p&lt；0.01)。因此，推测MA可能导致肾功能障碍，并对肾小管有一定损害。这种损伤可能与CPK从肌肉渗入血液有关。II组大鼠肾脏8-OH-dG阳性核数目增多，8-OH-dG定量增加(p&lt；0.01)。认为重复给药可能导致肾脏DNA氧化损伤。血钙明显降低(P<0.01)。推测肾功能损害与DNA氧化损伤有关。

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.