Trump B F, Berezesky I K
Department of Pathology, University of Maryland School of Medicine, Baltimore, USA.
New Horiz. 1996 Feb;4(1):139-50.
It has been known for some time that all pathophysiologic changes in shock and trauma have their basis at the cellular and molecular levels. These changes have been and continue to be studied in vivo in human patients and animal models and in vitro using a number of human and animal cell cultures. Cell injury and cell death have been studied in our laboratories for many years with reversible and irreversible cell responses having been characterized by functional, morphological, and biochemical methodologies. Recently, new technologies such as molecular biological experimentation for gene expression studies and digital imaging fluorescence microscopy to measure and localize ions, specifically the concentration of intracellular ionized calcium ([Ca2+i]), have been undertaken. Data from these studies have led us to propose a working hypothesis for a number of principle subcellular events that occur following a lethal injury. Dysregulation of [Ca2+i] is central to this hypothesis, since the effects of such dysregulation appear to affect many phenomena either positively or negatively. These phenomena are briefly discussed here. Much additional experimentation needs to be performed which should lead to further understanding of these events and to improved therapy, including modifiers of Ca(2+)-mediated events, new regulators of gene expression, and even gene therapy itself.
一段时间以来，人们已经知道休克和创伤中的所有病理生理变化都基于细胞和分子水平。这些变化过去一直在人类患者和动物模型中进行体内研究，并使用多种人类和动物细胞培养物进行体外研究，而且仍在继续。多年来，我们实验室一直在研究细胞损伤和细胞死亡，通过功能、形态和生化方法对可逆和不可逆的细胞反应进行了表征。最近，人们采用了新技术，如用于基因表达研究的分子生物学实验以及用于测量和定位离子（特别是细胞内游离钙([Ca2+]i)浓度）的数字成像荧光显微镜。这些研究的数据使我们对致命损伤后发生的一些主要亚细胞事件提出了一个工作假设。[Ca2+]i的失调是这一假设的核心，因为这种失调的影响似乎对许多现象产生了积极或消极的影响。这里简要讨论这些现象。还需要进行大量额外的实验，这应该会使我们对这些事件有更深入的了解，并改进治疗方法，包括钙介导事件的调节剂、新的基因表达调节剂，甚至基因治疗本身。
