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腎器官冰溫保存及相關(guān)基礎(chǔ)問(wèn)題研究

發(fā)布時(shí)間:2018-12-14 15:22
【摘要】:本文圍繞冰溫用于復(fù)雜生物組織保存的熱學(xué)機(jī)理這一基礎(chǔ)科學(xué)問(wèn)題展開研究,從細(xì)胞基礎(chǔ)實(shí)驗(yàn)至活體器官的成功移植,系統(tǒng)研究了復(fù)雜生物組織在冰溫條件下的傳熱傳質(zhì)特性。采用先進(jìn)的可視化手段動(dòng)態(tài)觀察并研究降溫過(guò)程中,細(xì)胞熱質(zhì)傳遞的現(xiàn)象規(guī)律。依據(jù)生物體真實(shí)形狀,對(duì)腎器官的三維瞬態(tài)溫度場(chǎng)進(jìn)行重構(gòu)。從新的角度、從宏微觀兩個(gè)層面上,對(duì)冰溫保存復(fù)雜生物組織的傳熱機(jī)理以及相關(guān)特征做出較為全面的認(rèn)識(shí)。 文中對(duì)冰點(diǎn)溫度以下的凍結(jié)過(guò)程進(jìn)行了分析,研究了細(xì)胞在凍結(jié)保存中由于不同的冷凍條件而產(chǎn)生的損傷及其原因。分別從細(xì)胞的滲透特性、機(jī)械擠壓損傷及胞內(nèi)冰這三個(gè)方面對(duì)細(xì)胞的損傷進(jìn)行了分析并探討了損傷產(chǎn)生的機(jī)理。 對(duì)于器官保存的研究?jī)?nèi)容主要包括:(1)建構(gòu)豬腎臟血管樹的物理模型并將其轉(zhuǎn)化為計(jì)算機(jī)可識(shí)別的數(shù)學(xué)模型,在此基礎(chǔ)上對(duì)腎臟冷灌注過(guò)程中的三維溫度場(chǎng)進(jìn)行了瞬態(tài)模擬。(2)為了研究復(fù)雜生物組織在降溫過(guò)程中,因溫度梯度較大而導(dǎo)致熱應(yīng)力,采用ANSYS Workbench多物理場(chǎng)協(xié)同計(jì)算模塊對(duì)腎臟組織的熱應(yīng)力進(jìn)行了數(shù)值模擬。在計(jì)算模型中將腎臟組織、微毛細(xì)血管簇等視為多孔介質(zhì)。在熱結(jié)構(gòu)耦合場(chǎng)計(jì)算中,將腎臟組織、動(dòng)靜脈血管壁視為固體介質(zhì),最后分析了不同灌注工況下,溫度場(chǎng)與熱應(yīng)力的相關(guān)性。對(duì)腎臟器官冷灌注過(guò)程進(jìn)行溫度場(chǎng)、熱應(yīng)力場(chǎng)數(shù)值重構(gòu),,目的在于探索冷激勵(lì)作用下,溫度以及降溫速率耦合作用引起的生物力學(xué)效應(yīng),分析這種微小的熱應(yīng)力或熱變形對(duì)細(xì)胞是否會(huì)造成物理?yè)p傷。(3)在冰溫技術(shù)應(yīng)用于器官延時(shí)保存的基礎(chǔ)研究方面,分別測(cè)量了腎細(xì)胞懸液,腎器官的冰點(diǎn)溫度等生物熱物性參數(shù)。比較了不同保存溫度對(duì)器官細(xì)胞活性的影響,冰溫保存與目前臨床應(yīng)用的保存溫度相比,降低了3-4℃。 本文提出的保存溫度(-0.8℃),可有效抑制組織細(xì)胞的基礎(chǔ)代謝率,減少細(xì)胞的能量消耗,降低低溫?fù)p傷引起的細(xì)胞凋亡。將所提出的保溫方法及保存溫度,施用于豬腎臟自體移植臨床試驗(yàn),取得了延時(shí)20小時(shí)以上的良好效果。 通過(guò)深層次研究冰溫范圍復(fù)雜生物組織宏微觀熱質(zhì)傳遞的特性,將生物傳熱與生物醫(yī)學(xué)兩個(gè)學(xué)科中的基礎(chǔ)研究關(guān)鍵問(wèn)題結(jié)合在一起,實(shí)現(xiàn)了理論凝練和技術(shù)創(chuàng)新。
[Abstract]:The thermal mechanism of ice temperature for the preservation of complex biological tissues is studied in this paper. The heat and mass transfer characteristics of complex biological tissues under ice temperature are systematically studied from the basic experiments of cells to the successful transplantation of living organs. The phenomena of heat and mass transfer in the process of cooling were observed and studied by advanced visual methods. According to the real shape of organism, the three-dimensional transient temperature field of renal organs was reconstructed. From a new point of view, from the macro and micro level, the heat transfer mechanism and related characteristics of ice temperature preservation complex biological tissue are comprehensively understood. In this paper, the freezing process below freezing temperature was analyzed, and the damage caused by different freezing conditions and its causes were studied. The mechanism of cell damage was analyzed from the aspects of cell permeability, mechanical extrusion injury and intracellular ice. The main contents of the research on organ preservation include: (1) constructing the physical model of porcine renal vascular tree and transforming it into a computer recognizable mathematical model. On this basis, the three-dimensional temperature field during cold perfusion of kidney was simulated. (2) in order to study the thermal stress of complex biological tissue during cooling process, the temperature gradient was large. The thermal stress of kidney tissue was numerically simulated by ANSYS Workbench multi-physical field cooperative calculation module. In the model, kidney tissues and microcapillaries are regarded as porous media. In the calculation of thermal structure coupling field, the renal tissue and the vascular wall of the arteriovenous vein are regarded as solid media. Finally, the correlation between temperature field and thermal stress under different perfusion conditions is analyzed. In order to explore the biomechanical effects of temperature and cooling rate coupling under cold excitation, the temperature field and thermal stress field of renal organs were reconstructed numerically during cold perfusion. Whether the tiny thermal stress or thermal deformation will cause physical damage to the cells. (3) in the basic research of ice temperature technology applied to the delayed preservation of organs, the renal cell suspensions were measured separately. The parameters of biological thermal properties such as freezing point temperature of renal organs. The effects of different preservation temperatures on organ and cell activity were compared. Compared with the current clinical storage temperature, the ice temperature was reduced by 3-4 鈩

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