儿茶酚胺在外伤性应激反应致大鼠MODS中作用机制的研究

During the forensic identification, the death as a result of non-lethal mechanical injury often occurred. Pure injury alone is not sufficient to cause death, so, what is the exact cause of death? This is the theoretic and technical problems demanding prompt solution on the identification of complex cause of death. Non-lethal mechanical injury effects on the organism, including the damage itself and the stress caused by injury. Whether stress response can lead to death has not yet been elucidated. Many studies indicated that the locus ceruleus norepinephrine system is mainly actived by physical stressors, which cause a significant increase in secretion of catecholamine (CA) in central nervous system and blood. The mechanism by which traumatic stress lead to MODS may involved the damage effect of CA. On the one hand, the toxic metabolites of CA can cause neuron and vascular endothelial cell injury, on the other hand, through binding its receptors, CA can induce apoptosis of neuron, cerebrovascular endothelial cell, myocardial cell and enteric epithelium as well as can contract blood vessels which may result in ischemic injury of tissue. Based on the present hypothesis, we plan to establish animal model, and to explore the mechanism underlying the role of catecholamine in MODS induced by traumatic stress by means of a variety of experimental method involved pathology, immunology and molecular biology. The present study will provide the theory basis and the technical method for complex cause identification in the death cases involved non-fatal mechanical injury and stress as well as provide the necessary technical support for effective executing the legal rule-prohibition of extorting confessions by torture in Criminal Procedure Law of the People's Republic of China .

在司法实践中经常遇到非致命性机械性损伤（如刑讯逼供）后发生MODS导致死亡的案件，其中就损伤本身不足以导致死亡，那么确切死因是什么？这是复杂死因鉴定方面亟待解决的理论和技术难题。此类损伤对机体的影响包括损伤本身和损伤引起的应激反应，应激反应与死亡是否具有因果关系，目前尚未阐明。外伤性应激发生后主要启动蓝斑-交感-肾上腺髓质轴，使中枢和血液中儿茶酚胺（CA）浓度升高，大量的CA可能通过其毒性代谢产物造成细胞损伤；也可能通过与受体结合诱导神经元、脑血管内皮细胞、心肌细胞和肠上皮细胞凋亡或收缩血管致组织缺血性损伤，导致MODS。根据以上科学假说，本项目拟建立动物模型，应用病理学、免疫学和分子生物学等多种方法研究CA在外伤性应激反应致大鼠MODS中的作用机制，为非致命性机械性损伤及应激参与的死亡案件的死因鉴定提供理论依据和技术方法，为有效执行《刑诉法》关于严禁刑讯逼供的规定提供必要的技术支持。

在司法实践中经常遇到非致命性机械性损伤（如交通事故、刑讯逼供等）后发生 MODS 导致死亡的案件，其中就损伤本身不足以导致死亡，那么确切死因是什么？这是复杂死因鉴定方面亟待解决的理论和技术难题。此类损伤对机体的影响包括损伤本身和损伤引起的应激反应，那么过度而持久的应激对重要组织器官有何影响？是否会加重损伤本身对机体产生的影响？目前尚未阐明。应激时，儿茶酚胺合成的限速酶酪氨酸羟化酶（TH）表达水平增加，儿茶酚胺（CA）分泌增多成为蓝斑-交感-肾上腺髓质系统产生中枢效应和外周效应的主要物质基础之一。文献报道，去甲肾上腺素和肾上腺素过度持久释放可以对组织细胞造成损伤，其作用机制主要有两个方面，第一、二者的代谢产物对组织细胞具有毒性作用；第二、通过受体机制引起血管收缩，造成组织缺血缺氧损伤或启动内质网应激、钙超载等改变。应激对重要组织器官的损伤作用机制是否与TH表达水平增加，去甲肾上腺素和肾上腺素分泌增多有关？目前未见报道。. 为阐明上述科学问题，本项目建立了挤压伤（损伤）和束缚应激（心理应激）的复合模型以模拟司法实践中非致命性机械性损伤和心理应激共同参与的案情，应用病理学、免疫学和分子生物学等多种方法研究了CA对蓝斑、孤束核、心肌组织及肠道屏障的损伤作用，证实束缚应激加重挤压伤大鼠蓝斑、孤束核、心肌组织及肠道屏障的损伤，导致MODS发生，其机制与TH表达增高和外周血CA浓度升高有关，研究结果表明，心理应激确实加重了损伤本身对机体产生的影响，造成中枢系统、心血管系统和肠道屏障组织损伤和功能障碍。该研究成果为非致命性机械性损伤和应激共同参与的死亡案件的死因鉴定提供理论依据和技术方法。