心肌細(xì)胞同步化節(jié)律的實(shí)驗(yàn)觀察及其動力學(xué)研究
本文選題:同步 + 網(wǎng)絡(luò); 參考:《陜西師范大學(xué)》2010年碩士論文
【摘要】: 生命活動的正常進(jìn)行依賴于心臟有節(jié)律的搏動。但是心臟的搏動節(jié)律不是均勻的,而是復(fù)雜的、非線性的。目前,人們認(rèn)識到心臟節(jié)律復(fù)雜性表現(xiàn)在三個層次上。整體心臟中,神經(jīng)、體液調(diào)節(jié)下的心臟節(jié)律的波動是內(nèi)源性的,并具有混沌的性質(zhì);在心臟內(nèi)興奮的傳導(dǎo)過程中,各級單元的失匹配會導(dǎo)致節(jié)律紊亂,如異位節(jié)律和折返性心率失常。在起搏節(jié)律上,竇房結(jié)中的細(xì)胞具有異質(zhì)性,它們耦合而成的同步化的心臟起搏節(jié)律也具有復(fù)雜性。心臟起搏節(jié)律的復(fù)雜性是心臟節(jié)律復(fù)雜性的重要原因。因此,研究同步化的起搏節(jié)律的形成是很必要的。心肌單細(xì)胞的搏動節(jié)律極不穩(wěn)定,節(jié)律變異系數(shù)大,較難從中發(fā)現(xiàn)可辨識的、統(tǒng)一的規(guī)律。同步化收縮的心肌細(xì)胞片在正常灌流液中呈現(xiàn)多種模式的搏動節(jié)律,周期節(jié)律(周期1、周期2、周期3)、陣發(fā)節(jié)律、整數(shù)倍節(jié)律和非周期節(jié)律等。以前,人們研究從單細(xì)胞到細(xì)胞團(tuán)的同步化形成過程都是在大的網(wǎng)絡(luò)中觀察幾個細(xì)胞從不同步搏動到同步化搏動的。但是這種對同步化形成過程的研究方法不能夠反映同步化形成過程的細(xì)節(jié)現(xiàn)象。本文將選取相鄰的兩個或三個細(xì)胞所在的小網(wǎng)絡(luò),通過兩個或三個細(xì)胞從不同步到同步化搏動的同步化過程的觀察來說明同步化形成的具體過程。此外,通過網(wǎng)絡(luò)的數(shù)學(xué)模型,仿真了在培養(yǎng)心肌細(xì)胞網(wǎng)絡(luò)中觀察到的已經(jīng)達(dá)到同步化的周期1節(jié)律,用以解釋心臟正常起步節(jié)律的形成機(jī)制。 本文通過活細(xì)胞工作站,采用光密度記錄手段,定位記錄兩個或三個細(xì)胞從不同步博動到同步搏動的過程。本研究還采用鈣熒光記錄手段,觀察到心肌細(xì)胞小網(wǎng)絡(luò)形成的同步化節(jié)律是多樣的,其中包括同步化程度高的周期一節(jié)律,但不是完全同步化的,有較小的平均相位差。為了研究心臟正常起搏節(jié)律的產(chǎn)生機(jī)制,我們運(yùn)用非線性動力學(xué)理論與方法。研究結(jié)果如下: 1.兩個或三個獨(dú)立搏動的細(xì)胞隨著培養(yǎng)時間的增加,也就是耦合強(qiáng)度的增加,會形成同步化的搏動節(jié)律。 2.同步初期的同步化節(jié)律是復(fù)雜多樣的。 3.搏動節(jié)律從不同步到同步化的過程是復(fù)雜多樣的。例如,在一些兩個細(xì)胞網(wǎng)絡(luò)中,部分搏動先達(dá)到同步,然后所有搏動達(dá)到同步。在三個細(xì)胞的網(wǎng)絡(luò)中,兩個細(xì)胞會先到達(dá)同步,然后三個細(xì)胞都達(dá)到同步。 4.隨著培養(yǎng)時間的增加和心肌細(xì)胞網(wǎng)絡(luò)中細(xì)胞個數(shù)的增加可以穩(wěn)定網(wǎng)絡(luò)的同步化節(jié)律為類似周期節(jié)律。 5.選用不同參數(shù)配置的Morris-Lecar(ML)模型模擬心肌細(xì)胞的異質(zhì)性,在鄰近耦合的異質(zhì)振子構(gòu)成的心肌細(xì)胞網(wǎng)絡(luò),振子參數(shù)遠(yuǎn)離Hopf分岔點(diǎn)時,可以仿真與實(shí)驗(yàn)相似的同步化周期一節(jié)律。 6.耦合強(qiáng)度越大,不同細(xì)胞的相位差就會越小但不為零;噪聲作用下的細(xì)胞節(jié)律間的相位差略有增大。 本研究結(jié)果不僅揭示了同步化節(jié)律形成過程中的節(jié)律變化特征,還提供生物系統(tǒng)的節(jié)律同步的實(shí)驗(yàn)例證。仿真結(jié)果提示耦合強(qiáng)度是節(jié)律同步的原因,而振子的異質(zhì)性和噪聲是產(chǎn)生相位差的原因。研究結(jié)果給出了心肌細(xì)胞網(wǎng)絡(luò)同步化周期一節(jié)律形成的動力學(xué)解釋。這就從理論上解釋了同步化周期節(jié)律的產(chǎn)生機(jī)制,有助于認(rèn)識正常心臟的起搏節(jié)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.
【學(xué)位授予單位】:陜西師范大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2010
【分類號】:R331.31
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