GENOMIC PREMODULATION OF POST-TRAUMATIC RECOVERY

内毒素(ETX)可以是一种致命剂，但它也可以用来启动 保护细胞、器官或动物以抵抗随后的伤害。虽然这件事 保护状态有一个不确定的机制，它是高度保守的 在这一点上，一种启动刺激保护另一种刺激，而且这种多样性 刺激似乎诱导了一种常见的基因模式的表达。 我们假设，多种类型的启动刺激可以分别 通过引起一种细胞或组织的表达而在治疗上启动 与后续保护相关的基因的共同程序 受伤。我们将在器官层面(孤立的)解决这一假设 心脏、肠道缺血模型)和基因水平 热休克早期反应基因的组织基因表达程序 蛋白质、抗氧化酶、生长因子和胎儿程序基因 对一系列病理和生理刺激作出反应。这 程序性反应将通过原位信使核糖核酸和 蛋白质杂交。组织基因注射及其后续模型 基因操作应该允许机械性的研究 前面的人物刻画。到目前为止的结果表明基因组是保守的 模仿胎儿状态对刺激的反应，这些刺激具有共同的 蛋白质合成依赖于保护诱导。骨骼肌 注射启动子/报告基因构建的表达 注射基因。最后，初步实验发现了一些相似之处。 大鼠与人相似刺激后心肌基因表达的差异。 从这些拟议的基本调查中获得的知识应导致 改进临床治疗。

Endotoxin (ETX) can be a lethal agent, but it also can be used to prime cells, organs, or animals to resist a subsequent injury. Though this state of protection has an undefined mechanism, it is highly conserved in that one priming stimulus protects against another, and that diverse stimuli appear to induce the expression of a common pattern of genes. We hypothesize that multiple types of priming stimuli can each therapeutically prime cells or tissues by causing the expression of a common program of genes which is related to protection from subsequent injury. We will address this hypothesis at the organ level (isolated heart, gut ischemia models) and gene levels by characterizing the program of tissue gene expression of early response genes, heat shock proteins, anti-oxidant enzymes, growth factors, and fetal program genes in response to a range of pathologic and physiologic stimuli. This programmed response will be localized within organs by in situ mRNA and protein hybridizations. Models of tissue gene injection and subsequent gene manipulation should allow mechanistic investigations of the preceding characterization. Results to date suggest a conserved genomic response mimicking the fetal state to stimuli which have in common the protein synthesis dependent induction of protection. Skeletal muscles injected with a promoter/reporter gene construct show expression of the injected gene. Finally, initial experiments suggest some parallels between rat and human myocardial gene expressions after similar stimuli. Knowledge gained from these proposed basic investigations should lead to improved clinical treatments.