【摘要】：心血管疾病是全球死亡率最高的疾病之一,其病理研究、早期預(yù)防和臨床診治是一項(xiàng)十分艱巨的工作。循環(huán)系統(tǒng)的數(shù)學(xué)模型可為心血管系統(tǒng)生理研究、心血管疾病的診斷和治療提供了一種有效的輔助手段。多尺度循環(huán)系統(tǒng)數(shù)學(xué)模型主要研究系統(tǒng)、器官和組織層次循環(huán)系統(tǒng)模型耦合中的多物理場問題和多種維度建模技術(shù)問題。建立多尺度的循環(huán)系統(tǒng)數(shù)學(xué)模型,能夠幫助定量分析循環(huán)系統(tǒng)各個層次上的生理和病理特性,提高心血管疾病的預(yù)防、診斷與治療水平。 本文的研究目標(biāo)是通過對不同層次循環(huán)系統(tǒng)建模中關(guān)鍵技術(shù)問題的研究,建立多尺度循環(huán)系統(tǒng)數(shù)學(xué)模型。具體完成了以下工作： 1、解決了循環(huán)系統(tǒng)多尺度模型研究中的關(guān)鍵技術(shù)問題,包括(1)仿真心率變異性的自主神經(jīng)系統(tǒng)模型技術(shù)；(2)提高一維(One-Dimensional,1D)微循環(huán)模型仿真效率的數(shù)值計(jì)算技術(shù)；(3)整體循環(huán)系統(tǒng)與微循環(huán)系統(tǒng)的耦合技術(shù)。 2、建立了整體循環(huán)系統(tǒng)與自主神經(jīng)系統(tǒng)耦合模型,基于該模型提出了一種表征副交感神經(jīng)活動的特異性參數(shù)。應(yīng)用臨床數(shù)據(jù)初步驗(yàn)證了該參數(shù)的有效性,并基于模型分析了其生理機(jī)制。 3、建立了基于大鼠腸系膜實(shí)驗(yàn)數(shù)據(jù)的微循環(huán)系統(tǒng)1D模型,仿真了血流脈動性的衰減特性。基于模式動物實(shí)驗(yàn)驗(yàn)證了模型的有效性。應(yīng)用該模型發(fā)現(xiàn)微血管的阻力與順應(yīng)性是血流脈動性衰減的主要原因。 4、基于結(jié)構(gòu)參數(shù)耦合了整體循環(huán)與微循環(huán)系統(tǒng)模型,仿真發(fā)現(xiàn)微循環(huán)結(jié)構(gòu)性病變會改變整體血壓水平。仿真結(jié)果還表明,高血壓情況下外周血壓脈動性降低,并影響微循環(huán)功能。 在上述工作中,本文研究的創(chuàng)新點(diǎn)在于： 1、提出了基于血管阻力及順應(yīng)性耦合的多尺度模型技術(shù),有效地解決了整體循環(huán)與微循環(huán)系統(tǒng)模型結(jié)合的問題,為仿真研究血流動力學(xué)與功能特性的融合提供了有益的探索。 2、基于結(jié)合自主神經(jīng)調(diào)節(jié)機(jī)制的整體循環(huán)模型研究,提出了一種改進(jìn)的心率減速能力參數(shù),并借助模型闡明了算法改進(jìn)的機(jī)理,為促進(jìn)自主神經(jīng)系統(tǒng)評價指標(biāo)的臨床應(yīng)用提供了一種新的方法。 3、提出了1D微循環(huán)系統(tǒng)建模中高效的數(shù)值計(jì)算方法,所建立的模型可系統(tǒng)地仿真血流脈動性衰減現(xiàn)象,改變了微循環(huán)血流脈動性衰減機(jī)制研究中缺乏技術(shù)手段的現(xiàn)狀,為研究微循環(huán)中血流脈動性介導(dǎo)的機(jī)械信號轉(zhuǎn)導(dǎo)過程提供了嶄新的平臺。 本文所建立的多尺度循環(huán)系統(tǒng)數(shù)學(xué)模型為循環(huán)系統(tǒng)生理和病理研究提供了有效的定量研究技術(shù)平臺,待其完善并應(yīng)用后將有益于促進(jìn)心血管疾病基礎(chǔ)研究,提升國民心血管健康水平。
[Abstract]:Cardiovascular disease is one of the highest mortality diseases in the world. Its pathological research, early prevention and clinical diagnosis and treatment is a very difficult task. The mathematical model of circulatory system can provide an effective auxiliary means for the study of cardiovascular system physiology and the diagnosis and treatment of cardiovascular diseases. The mathematical model of multi-scale circulation system mainly studies the multi-physical field problem and multi-dimensional modeling technology in the coupling of system, organ and tissue hierarchical circulation system model. The establishment of multi-scale mathematical model of circulatory system can help to quantitatively analyze the physiological and pathological characteristics of circulatory system at all levels and improve the prevention, diagnosis and treatment of cardiovascular diseases. The research goal of this paper is to establish the mathematical model of multi-scale circulation system by studying the key technical problems in the modeling of different levels of circulation system. The main work is as follows: 1. The key technical problems in the study of multi-scale model of circulatory system are solved, including (1) the autonomic nervous system model technology to simulate heart rate variability; (2) the numerical calculation technology to improve the simulation efficiency of one-dimensional (One-Dimensional,1D) microcirculatory model, and (3) the coupling technology of the whole circulation system and the microcirculatory system. 2. A coupling model of global circulatory system and autonomic nervous system was established, and a specific parameter to characterize parasympathetic nerve activity was proposed based on the model. The validity of the parameter was preliminarily verified by clinical data, and its physiological mechanism was analyzed based on the model. 3. The 1D model of microcirculatory system based on rat mesenteric experimental data was established, and the attenuation characteristics of blood flow pulsation were simulated. The effectiveness of the model is verified by model-based animal experiments. Using this model, it is found that the resistance and compliance of microvessels are the main reasons for the pulsatile attenuation of blood flow. 4. Based on the structural parameters, the model of global circulation and microcirculatory system is coupled, and it is found that the structural lesion of microcirculation will change the level of global blood pressure. The simulation results also show that the pulsation of peripheral blood pressure decreases and affects the function of microcirculatory in the case of hypertension. In the above work, the innovations of this paper are as follows: 1. A multi-scale model technology based on the coupling of vascular resistance and compliance is proposed, which effectively solves the problem of the combination of the whole circulation and the microcirculatory system model. It provides a useful exploration for the simulation study of the fusion of hemodynamics and functional characteristics. 2. Based on the research of global circulation model combined with autonomic nerve regulation mechanism, an improved heart rate deceleration ability parameter is proposed, and the mechanism of algorithm improvement is expounded with the help of the model. It provides a new method for promoting the clinical application of autonomic nervous system evaluation index. 3. An efficient numerical calculation method in 1D microcirculatory system modeling is proposed. The established model can systematically simulate the phenomenon of blood flow pulsation attenuation, which changes the present situation of the lack of technical means in the study of the mechanism of circulatory blood flow pulsation attenuation. It provides a new platform for studying the mechanical signal transduction process mediated by blood flow pulsation in microcirculation. The mathematical model of multi-scale circulatory system established in this paper provides an effective quantitative research technical platform for physiological and pathological research of circulatory system, and when it is perfected and applied, it will be beneficial to promote the basic research of cardiovascular diseases. Improve the level of cardiovascular health of the people.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2013
【分類號】：R311

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