Study for the induction mechanism of the shock-Investigation on the burn shock model-

休克诱发机制研究-烧伤休克模型研究-

• 批准号: 17590590
• 负责人: KITA Toshiro
• 金额: $ 1.98万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590590/
• 关键词: Shock; Cause of death; Marker; Polymorphonuclear leukocytes; Apoptosis; Burn; p38MAPK; Cytokine; 心臓; 臓器障害; MAPK; サイトカイン

We approached to the induction mechanism of shock, and we investigated what etiology induced these morphological changes after shock in order to identify shock as the cause of death. The aim of this experiment sought to explain the cause of cardiac dysfunction following burn shock and search a marker of shock. So, we investigated the induction of inflammatory cells (PMNs), apoptosis and Hsp70 of the myocardial tissue as a marker of shock. Added to this, we approached the role of p38MAPK on the cardiac failure after burn injury using a specific inhibitor of p38MAPK (FR167653).At 2 hours after burn, we observed the induction of p38MAPK and myocardial apoptosis after burn injury using infant rat model. Subsequently, activation of cytokine (TNF-α) and the appearance of inflammatory cells (PMNs) are observed at 6 hours after burn. The inductions of Hsp70 in the myocardial tissue after burn are not clearly observed. FR167653 prevented the activation of p38MAPK in the heart and, finally, prevented burn-induced heart failure. So we identified the pathophysiologic role of the p38MAPK pathway in the development of heart failure after burn.Forensic practiceOur experimental burn shock data showed the induction of apoptosis and PMNs after burn injury. Consequently, we used the apoptosis and PMNs staining method, and we immunohistochemically investigated several organs of our practical autopsy cases to detect the appearance of apoptosis and PMNs as a marker of shock induction. We compared the hemorrhagic shock with other causes of death, such as blood loss, asphyxia, drawing and head injury. In every organ, a significant induction of apoptosis and PMNs were observed in the hemorrhagic shock compared to the other causes of death.Therefore, detecting the induction of apoptosis and PMNs as a marker of shock is a very useful and significant method for judging the cause of death in forensic practice.

我们探讨了休克的诱导机制，并探讨了是什么原因导致了休克后的这些形态变化，以确定休克是死亡的原因。本实验的目的是解释烧伤休克后心功能障碍的原因，并寻找休克的标志物。因此，我们研究了心肌组织炎性细胞(PMN)的诱导、细胞凋亡和HSP70作为休克的标志物。此外，我们使用p38MAPK的特异性抑制剂(FR167653)探讨了p38MAPK在烧伤后心力衰竭中的作用。在烧伤后2小时，我们用幼鼠烧伤模型观察了p38MAPK的诱导和心肌细胞凋亡。随后在烧伤后6h观察细胞因子(肿瘤坏死因子-α)的激活和炎性细胞(PMN)的出现。烧伤后心肌组织中热休克蛋白70的诱导作用尚不清楚。FR167653阻止了心脏中p38MAPK的激活，最终防止了烧伤所致的心力衰竭。因此，我们确定了p38MAPK通路在烧伤后心力衰竭发展过程中的病理生理作用。法医实践我们的实验性烧伤休克数据显示，烧伤后细胞凋亡和中性粒细胞的诱导。因此，我们采用了细胞凋亡和中性粒细胞染色的方法，并对实际尸检病例的几个器官进行了免疫组织化学研究，以检测细胞凋亡的出现情况，并将中性粒细胞作为休克诱导的标志。我们将失血性休克与其他死因进行了比较，如失血、窒息、拉伤和头部损伤。与其他死因相比，失血性休克时各器官均有明显的细胞凋亡和中性粒细胞的诱导，因此，检测细胞凋亡和中性粒细胞作为休克的标志物在法医实践中是一种非常有用和有意义的死因判断方法。