心肌细胞同步化节律的实验观察及其动力学研究

发布时间：2018-04-28 04:47

本文选题：同步 + 网络　；参考：《陕西师范大学》2010年硕士论文

【摘要】： 生命活动的正常进行依赖于心脏有节律的搏动。但是心脏的搏动节律不是均匀的,而是复杂的、非线性的。目前,人们认识到心脏节律复杂性表现在三个层次上。整体心脏中,神经、体液调节下的心脏节律的波动是内源性的,并具有混沌的性质；在心脏内兴奋的传导过程中,各级单元的失匹配会导致节律紊乱,如异位节律和折返性心率失常。在起搏节律上,窦房结中的细胞具有异质性,它们耦合而成的同步化的心脏起搏节律也具有复杂性。心脏起搏节律的复杂性是心脏节律复杂性的重要原因。因此,研究同步化的起搏节律的形成是很必要的。心肌单细胞的搏动节律极不稳定,节律变异系数大,较难从中发现可辨识的、统一的规律。同步化收缩的心肌细胞片在正常灌流液中呈现多种模式的搏动节律,周期节律(周期1、周期2、周期3)、阵发节律、整数倍节律和非周期节律等。以前,人们研究从单细胞到细胞团的同步化形成过程都是在大的网络中观察几个细胞从不同步搏动到同步化搏动的。但是这种对同步化形成过程的研究方法不能够反映同步化形成过程的细节现象。本文将选取相邻的两个或三个细胞所在的小网络,通过两个或三个细胞从不同步到同步化搏动的同步化过程的观察来说明同步化形成的具体过程。此外,通过网络的数学模型,仿真了在培养心肌细胞网络中观察到的已经达到同步化的周期1节律,用以解释心脏正常起步节律的形成机制。本文通过活细胞工作站,采用光密度记录手段,定位记录两个或三个细胞从不同步博动到同步搏动的过程。本研究还采用钙荧光记录手段,观察到心肌细胞小网络形成的同步化节律是多样的,其中包括同步化程度高的周期一节律,但不是完全同步化的,有较小的平均相位差。为了研究心脏正常起搏节律的产生机制,我们运用非线性动力学理论与方法。研究结果如下： 1.两个或三个独立搏动的细胞随着培养时间的增加,也就是耦合强度的增加,会形成同步化的搏动节律。 2.同步初期的同步化节律是复杂多样的。 3.搏动节律从不同步到同步化的过程是复杂多样的。例如,在一些两个细胞网络中,部分搏动先达到同步,然后所有搏动达到同步。在三个细胞的网络中,两个细胞会先到达同步,然后三个细胞都达到同步。 4.随着培养时间的增加和心肌细胞网络中细胞个数的增加可以稳定网络的同步化节律为类似周期节律。 5.选用不同参数配置的Morris-Lecar(ML)模型模拟心肌细胞的异质性,在邻近耦合的异质振子构成的心肌细胞网络,振子参数远离Hopf分岔点时,可以仿真与实验相似的同步化周期一节律。 6.耦合强度越大,不同细胞的相位差就会越小但不为零；噪声作用下的细胞节律间的相位差略有增大。本研究结果不仅揭示了同步化节律形成过程中的节律变化特征,还提供生物系统的节律同步的实验例证。仿真结果提示耦合强度是节律同步的原因,而振子的异质性和噪声是产生相位差的原因。研究结果给出了心肌细胞网络同步化周期一节律形成的动力学解释。这就从理论上解释了同步化周期节律的产生机制,有助于认识正常心脏的起搏节律。
[Abstract]:The normal progression of life activities depends on the rhythmic beat of the heart. But the rhythm of the heart is not uniform, but complex and nonlinear. At present, it is realized that the complexity of the heart rhythm is shown on three levels. The fluctuation of the heart rhythm under the regulation of the whole heart, nerve and body fluid is endogenous and has chaos. In the course of conduction in the heart, the mismatch of the units at all levels leads to rhythmic disorders, such as ectopic rhythm and reentrant arrhythmia. In the rhythm of the pacing, the cells in the sinoatrial node are heterogeneous, and their coupled cardiac pacing rhythm is complex. The complexity of the cardiac pacing rhythm is the heart. It is essential to study the complexity of rhythms. Therefore, it is necessary to study the formation of synchronized pacing rhythm. The pulsation rhythm of the single cell of the myocardium is extremely unstable, the coefficient of rhythm variation is large, and it is difficult to find the identifiable and unified law. The synchronized systolic myocardial cell slices present a variety of patterns of pulsation rhythm in the normal perfusion fluid. Rhythms (cycle 1, cycle 2, cycle 3), formation rhythm, integer and non periodic rhythms, etc. before, the synchronization of cells from single cells to cell groups was studied in a large network to observe a few cells from synchronized pulsating to synchronized pulsation. However, the method of research on the synchronization process could not be reflected. The details of the synchronization process. This paper will select the small networks of two or three adjacent cells to illustrate the synchronization process through the observation of the synchronization of two or three cells from sync to synchronized pulsation. In addition, the network's digital model is used to simulate the cultured cardiac cell network. The 1 cycle of synchronization has been observed to explain the formation mechanism of normal cardiac rhythm.
In this study, the process of recording two or three cells from unsynchronized motion to synchronous pulsation was recorded by means of light density recording by the live cell workstation. In order to study the mechanism of the normal pacing rhythm of the heart, we use the theory and method of nonlinear dynamics. The results are as follows:
1. two or three independent beating cells increase with the increase of culture time, that is, the increase of coupling strength will form synchronized pulsatility rhythm.
2. the synchronization rhythm at the beginning of synchronization is complex and diverse.
3. the process of pulsating rhythms from sync to synchronization is complex and diverse. For example, in some two cell networks, partial pulsation reaches synchrony first, and all pulsation reaches synchronization. In the network of three cells, two cells will reach synchronization first, and then the three cells are synchronized.
4. with the increase of culture time and the increase of the number of cells in the cardiac myocyte network, the synchronization rhythm of the stable network is similar to that of the periodic rhythm.
5. the Morris-Lecar (ML) model with different parameters is used to simulate the heterogeneity of cardiac myocytes. In the myocardial cell network formed by the adjacent coupled heterostructure, the oscillator parameters are far away from the Hopf bifurcation point, and the synchronization of the periodic one rhythm can be simulated.
6. the larger the coupling intensity, the smaller the phase difference of different cells, but not zero. The phase difference between the cell rhythms under noise is slightly increased.
The results of this study not only reveal the characteristics of rhythmic changes in the formation of synchronized rhythms, but also provide an experimental example of rhythmic synchronization in biological systems. The simulation results suggest that the coupling strength is the cause of rhythm synchronization, and the heterogeneity and noise of the oscillator are the causes of the phase difference. The results of the study give the synchronization week of the myocardial cell network. The kinetic explanation for the formation of the first period rhythm explains the generation mechanism of the synchronized periodic rhythm theoretically, and helps to understand the pacing rhythm of the normal heart.

【学位授予单位】：陕西师范大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R331.31

【参考文献】