凝血瀑布机制中蛋白C作用的动力学模型研究

Dynamic Model Analysis of Protein C in Blood Coagulation Mechanism

凝血过程涉及到一系列蛋白因子的反应,上一级的活性蛋白因子裂解下级的蛋白质,使其成为活性的蛋白质,从而使反应继续而形成反应瀑布机制,在凝血反应核心反馈过程中,蛋白C起着至关重要的调节作用。本研究主要探讨在凝血过程中蛋白C的激活和失活过程,活性蛋白C对因子V的作用以及对整个凝血系统的影响。在生理实验的基础上,建立关于凝血蛋白C作用的非线性数学模型,通过系统的定态平衡分析,从理论上证明存在外源性路径启动的触发阈值;通过动态解的数值模拟,研究蛋白C的作用。结果证实,蛋白C的缺乏对整个凝血系统的影响是微弱的,是否缺乏蛋白C对系统的启动阈值没有影响;但是当蛋白C过量时,IIa的浓度随着时间的延长趋于零,预示凝血系统不能正常启动,蛋白C对IIa有很强抑制作用。以上结果将对血液学理论与临床血液学研究提供有益的启示,也展现出模型化方法对研究凝血系统的预测性能力。

In the process of blood coagulation, a serial reaction of protein factors is involved. The active protein on the first level decomposes the subordinate protein, that causes the subordinate protein to become the active protein, and causes the response to continue forming the response waterfall mechanism. During the essential process of feed back reaction about blood coagulation, protein C plays an important role. This article investigates the effect of protein C on factor V and whole blood coagulation system during the being- activated and being-deactivated processes of blood coagulation. Based on the physiological experiment, a non- linear mathematic model of blood coagulation cascade was put forward. According to the fixed point theory, stability analysis was completed. We approved that there was a threshold value in the extrinsic blood coagulation cascade. We simulated numerically and found the effect of protein C on the whole blood coagulation. It was indicated that lack of protein C little affect the whole blood coagulation. Whether protein C was lack or not did not influence the threshold value of initiated stage of blood coagulation. However when the concentration of protein C was excessive, the concentration of IIa reduced to zero along with time going, that indicated whole system could not be initiated normally and influence of protein C to IIa was very strong. These results above provide kind of beneficial enlightenment to the hematology theory and clinical research, also show the modeling method is useful and available for providing beneficial help to the blood coagulation studies.