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例法医尸检中检测到甲基苯丙胺（MA）的肾脏进行了免疫组织化学研究。72.7%的患者肌红蛋白呈阳性。怀疑MA损伤了骨骼肌。80%的hsp70阳性病例为肌红蛋白阳性。在8- oh - dg阳性、4- hne阳性和sod阳性病例中，分别有60.0%、88.6%和77.8%的患者出现肌红蛋白。因此，怀疑肌红蛋白诱导氧化损伤。这些物质的免疫反应性与MA浓度的关系无统计学意义。本研究提示肌红蛋白、HSP70、8-OH-dG、4-HNE和SOD的免疫组化染色有助于推测MA滥用者死亡前的情况。2004年，我们研究了MA对大鼠肾脏的影响。单次给药组（I组）和多次给药组（II组）分别为急性模型和亚急性或慢性模型。免疫组织化学观察到几种细胞损伤标志物。然后测定肾功能指标和血矿物质含量。同时分析血中肌红蛋白和肌酸酐磷酸激酶（CPK）。在I组中，泛素免疫反应性仅在肾小管中增强。肌酐升高，K、Ca、P降低（P <0.01）。CPK显著升高（p<0.01）。因此，我们怀疑MA可能引起肾功能不全，并对肾小管造成一定损害。这种损伤可能与CPK从肌肉渗漏到血液有关。ⅱ组大鼠肾组织8-OH-dG阳性细胞核数量增多，8-OH-dG数量增多（p<0.01）。认为重复给药可能引起肾脏DNA氧化损伤。血钙显著降低（p<0.01）。怀疑与DNA氧化损伤有关的肾功能不全。

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.