Zhao Dong, Ishikawa Takaki, Quan Li, Li Dong-Ri, Michiue Tomomi, Yoshida Chiemi, Komatu Ayumi, Chen Jian-Hua, Zhu Bao-Li, Maeda Hitoshi
Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan.
Forensic Sci Int. 2008 May 20;177(2-3):176-83. doi: 10.1016/j.forsciint.2007.12.004. Epub 2008 Feb 19.
Glucose transporter 1 (GLUT1) and vascular endothelial growth factor (VEGF) have been established as being responsible for cellular adaptation to oxygen deficiency in tissue ischemia and hypoxia mediated by hypoxia-inducible factor 1. We hypothesized that mRNA quantification of these factors in autopsy tissue specimens could have diagnostic significance for investigating the pathology of death, especially after injury. Various cases (total, n=119; less than 48h postmortem) were examined, including fatal blunt injury (n=71) and sharp instrument injury (n=18), as well as asphyxia (strangulation/hanging, n=12) and acute myocardial infarction/ischemia (n=18) as controls. Quantification of mRNA by TaqMan real-time RT-PCR and immunostaining were performed for GLUT1 and VEGF in lung, kidney, and skeletal muscle specimens. The postmortem interval showed no significant influence on the relative quantification of mRNA during the early postmortem period. Characteristic results were found in blunt injury cases: both GLUT1 and VEGF mRNAs decreased in the lung but increased in the skeletal muscle depending on survival time. In the kidney, subacute deaths showed higher GLUT1 mRNA levels compared with acute deaths from blunt injury, but no significant change was found for VEGF mRNA. Immunohistochemistry showed visually predominant GLUT1 immunoreactivity in the renal cortex for cases with a longer survival time, coincident with the results at the mRNA level. Tissue-specific differences in mRNA quantification of GLUT1 and VEGF shed light on tissue ischemia/hypoxia and subsequent tissue-dependent pathophysiological changes leading to death after injury.
葡萄糖转运蛋白1(GLUT1)和血管内皮生长因子(VEGF)已被证实负责细胞在由缺氧诱导因子1介导的组织缺血和缺氧过程中对缺氧的适应。我们推测,在尸检组织标本中对这些因子进行mRNA定量分析对于研究死亡病理,尤其是损伤后的死亡病理可能具有诊断意义。我们检查了各种案例(总计n = 119;死后不到48小时),包括致命钝器伤(n = 71)和锐器伤(n = 18),以及作为对照的窒息(勒死/上吊,n = 12)和急性心肌梗死/缺血(n = 18)。通过TaqMan实时逆转录PCR对肺、肾和骨骼肌标本中的GLUT1和VEGF进行mRNA定量分析,并进行免疫染色。在死后早期,死后间隔时间对mRNA的相对定量没有显著影响。在钝器伤案例中发现了特征性结果:根据存活时间,GLUT1和VEGF的mRNA在肺中均下降,但在骨骼肌中升高。在肾脏中,与钝器伤急性死亡相比,亚急性死亡显示出更高的GLUT1 mRNA水平,但VEGF mRNA未发现显著变化。免疫组织化学显示,存活时间较长的病例在肾皮质中GLUT1免疫反应性在视觉上占主导地位,这与mRNA水平的结果一致。GLUT1和VEGF的mRNA定量分析中的组织特异性差异揭示了组织缺血/缺氧以及随后导致损伤后死亡的组织依赖性病理生理变化。