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腎器官冰溫保存及相關(guān)基礎(chǔ)問題研究

發(fā)布時間:2018-12-14 15:22
【摘要】:本文圍繞冰溫用于復雜生物組織保存的熱學機理這一基礎(chǔ)科學問題展開研究,從細胞基礎(chǔ)實驗至活體器官的成功移植,系統(tǒng)研究了復雜生物組織在冰溫條件下的傳熱傳質(zhì)特性。采用先進的可視化手段動態(tài)觀察并研究降溫過程中,細胞熱質(zhì)傳遞的現(xiàn)象規(guī)律。依據(jù)生物體真實形狀,對腎器官的三維瞬態(tài)溫度場進行重構(gòu)。從新的角度、從宏微觀兩個層面上,對冰溫保存復雜生物組織的傳熱機理以及相關(guān)特征做出較為全面的認識。 文中對冰點溫度以下的凍結(jié)過程進行了分析,研究了細胞在凍結(jié)保存中由于不同的冷凍條件而產(chǎn)生的損傷及其原因。分別從細胞的滲透特性、機械擠壓損傷及胞內(nèi)冰這三個方面對細胞的損傷進行了分析并探討了損傷產(chǎn)生的機理。 對于器官保存的研究內(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)化為計算機可識別的數(shù)學模型,在此基礎(chǔ)上對腎臟冷灌注過程中的三維溫度場進行了瞬態(tài)模擬。(2)為了研究復雜生物組織在降溫過程中,因溫度梯度較大而導致熱應力,采用ANSYS Workbench多物理場協(xié)同計算模塊對腎臟組織的熱應力進行了數(shù)值模擬。在計算模型中將腎臟組織、微毛細血管簇等視為多孔介質(zhì)。在熱結(jié)構(gòu)耦合場計算中,將腎臟組織、動靜脈血管壁視為固體介質(zhì),最后分析了不同灌注工況下,溫度場與熱應力的相關(guān)性。對腎臟器官冷灌注過程進行溫度場、熱應力場數(shù)值重構(gòu),目的在于探索冷激勵作用下,溫度以及降溫速率耦合作用引起的生物力學效應,分析這種微小的熱應力或熱變形對細胞是否會造成物理損傷。(3)在冰溫技術(shù)應用于器官延時保存的基礎(chǔ)研究方面,分別測量了腎細胞懸液,腎器官的冰點溫度等生物熱物性參數(shù)。比較了不同保存溫度對器官細胞活性的影響,冰溫保存與目前臨床應用的保存溫度相比,降低了3-4℃。 本文提出的保存溫度(-0.8℃),,可有效抑制組織細胞的基礎(chǔ)代謝率,減少細胞的能量消耗,降低低溫損傷引起的細胞凋亡。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,取得了延時20小時以上的良好效果。 通過深層次研究冰溫范圍復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)學兩個學科中的基礎(chǔ)研究關(guān)鍵問題結(jié)合在一起,實現(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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