GENOMIC PREMODULATION OF POST-TRAUMATIC RECOVERY

内毒素（ETX）可以是一种致死剂，但它也可以用于引发 细胞、器官或动物来抵抗随后的伤害。 虽然这 保护状态具有未定义的机制，它是高度保守的 一种启动刺激可以保护另一种， 刺激物似乎诱导一种共同的基因模式的表达。 我们假设，多种类型的启动刺激， 通过引起一种或多种免疫原性蛋白的表达来治疗性地引发细胞或组织。 基因的共同程序，这与保护免受随后的 损伤 我们将在器官水平上解决这个假设（孤立的 心脏，肠缺血模型）和基因水平， 早期反应基因的组织基因表达程序，热休克 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mRNA定位在器官内， 蛋白质杂交。 组织基因注射模型及后续 基因操作应该允许对基因组的机制进行研究。 前特征。 迄今为止的结果表明， 模拟胎儿状态的反应，以刺激具有共同的 蛋白质合成依赖的保护诱导。 骨骼肌 注射了启动子/报告基因构建体的小鼠， 注入基因 最后，初步实验表明， 大鼠和人类心肌基因表达之间的差异。 从这些拟议的基础调查中获得的知识应该会导致 改善临床治疗。

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.