A nonlinear dynamical theory of cell injury
A nonlinear dynamical theory of cell injury
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DOI：
10.1038/jcbfm.2012.10
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发表时间：
2012-06-01
影响因子：
6.3
通讯作者：
Huang, Sui
中科院分区：
文献类型：
--
作者：
De Gracia, Donald J.;Huang, Zhi-Feng;Huang, Sui
多因素损伤，如缺血、创伤等，已经被证明顽固地难以临床治疗，尽管康复或死亡的二元结果。这可能部分是由于缺乏正式的细胞损伤方法。我们提出了一个非线性常微分方程的最小系统描述的细胞损伤动力学理论。损伤驱动的总损伤和总诱导的应激反应之间的相互拮抗作用产生代表恢复或死亡的吸引子。在一系列损伤程度上求解定义了一个“损伤过程”，其中包含一个定义明确的恢复和死亡之间的临界点。通过这个模型，治疗学是将一个系统从一个倾向于死亡的轨道转向一个倾向于生存的轨道。该模型合理地解释了为什么基于实验室的治疗往往在临床上失败。当致命伤害接近临界点时，生存结果很容易实现，但随着伤害程度的增加，生存结果变得越来越困难，并且可挽救的伤害有上限。该模型为细胞损伤提供了新的见解，可能有助于克服阻碍多因素条件临床有效疗法发展的障碍，如脑缺血。Journal of Cerebral Blood Flow & Metabolism（2012）32，1060-1013; doi：10.1038/jcbfm.2012.10; 2012年3月7日在线发表
Multifactorial injuries, such as ischemia, trauma, etc., have proven stubbornly elusive to clinical therapeutics, in spite of the binary outcome of recovery or death. This may be due, in part, to the lack of formal approaches to cell injury. We present a minimal system of nonlinear ordinary differential equations describing a theory of cell injury dynamics. A mutual antagonism between injury-driven total damage and total induced stress responses gives rise to attractors representing recovery or death. Solving across a range of injury magnitudes defines an 'injury course' containing a well-defined tipping point between recovery and death. Via the model, therapeutics is the diverting of a system on a pro-death trajectory to a pro-survival trajectory on bistable phase planes. The model plausibly explains why laboratory-based therapies have tended to fail clinically. A survival outcome is easy to achieve when lethal injury is close to the tipping point, but becomes progressively difficult as injury magnitudes increase, and there is an upper limit to salvageable injuries. The model offers novel insights into cell injury that may assist in overcoming barriers that have prevented development of clinically effective therapies for multifactorial conditions, as exemplified by brain ischemia. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1060-1013; doi:10.1038/jcbfm.2012.10; published online 7 March 2012