外扰作用下细胞内稳态鲁棒性实验研究

Experiments of Homeostasis Robustness on the Cells after Disturbance

内稳态是一种重要的生理现象,是生物反应动态平衡的结果。以内皮细胞为对象,用H2O2作为外源扰动剂,建立一种外扰作用下细胞内钙稳态鲁棒性的分析方法,包括以控制理论Lyapunov及鲁棒性理论为基础的扰动前稳态点和稳定域、扰动后状态转移和稳定鲁棒域。通过对照和1、10、305、0、100μmol/L 5种不同剂量H2O2扰动人脐静脉内皮细胞实验,获得6组48个细胞(每组8个细胞)内钙浓度数据,分析细胞内钙稳态和扰动剂稳定鲁棒域。结果表明:(1)受扰动前,细胞内钙稳态点从0.709到8.189不等,表现出明显的个体差异;稳定域半径r从0.654到2.650不等,表明细胞稳定性较好,可以排除后续扰动实验中细胞不稳定对结果的影响。(2)受扰动后,细胞内钙初态对细胞受扰后内钙状态转移影响不大。(3)H2O2为1μmol/L时可使4个细胞发生渐进稳定,为10μmol/L时可使2个细胞渐近稳定,为30μmol/L时可使1个细胞渐近稳定,说明稳定鲁棒域与细胞个体有关;该内皮细胞种族的内钙稳态鲁棒域至少在50μmol/L以内。结论表明:利用控制理论方法设计生物鲁棒性实验,并实现细胞内钙稳态定量化分析,是一种有效的方法。

Homeostasis,as a result of balanced dynamic biological action,is an important physiological phenomenon.Based on Lyapunov theory and robustness theory,we established a series of methods such as： stability and its domain of homeostasis during pre-disturbance and inner calcium state transfer and stability robust domain of H2O2 after pro-disturbance.Experiments on 6 groups of endothelial cells（8 cells in each group） were carried on,one group as control,the other five under the disturbance of H2O2 at 1,10,30,50,100 μmol/L.The concentrations of inner calcium were obtained for quantitative analyses of homeostasis and robust domain of H2O2.Results showed that：（1） the steady states of inner calcium distributed from 0.709 to 8.189,indicating significant individual difference for stability,while radiuses of steady area from 0.654 to 2.650,indicating the good stability and excluding the possible influence of the following disturbance;（2） inner calcium state transfer after pro-disturbance was hardly affected by initial state of inner calcium;（3） 1 μmol/L H2O2 might induce asymptotic stability for 4 cells,10 μmol/L for 2 cells and 30 μmol/L for 1 cell,suggesting that the steady robust domain related to the individual cell itself and the domain for this population of endothelial cells was at least 50 μmol/L.We conclude that designing biological robustness by control theory is an effective method to realize quantitatively analysis of inner calcium homeostasis.