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肾器官冰温保存及相关基础问题研究

发布时间:2018-12-14 15:22
【摘要】:本文围绕冰温用于复杂生物组织保存的热学机理这一基础科学问题展开研究,从细胞基础实验至活体器官的成功移植,系统研究了复杂生物组织在冰温条件下的传热传质特性。采用先进的可视化手段动态观察并研究降温过程中,细胞热质传递的现象规律。依据生物体真实形状,对肾器官的三维瞬态温度场进行重构。从新的角度、从宏微观两个层面上,对冰温保存复杂生物组织的传热机理以及相关特征做出较为全面的认识。 文中对冰点温度以下的冻结过程进行了分析,研究了细胞在冻结保存中由于不同的冷冻条件而产生的损伤及其原因。分别从细胞的渗透特性、机械挤压损伤及胞内冰这三个方面对细胞的损伤进行了分析并探讨了损伤产生的机理。 对于器官保存的研究内容主要包括:(1)建构猪肾脏血管树的物理模型并将其转化为计算机可识别的数学模型,在此基础上对肾脏冷灌注过程中的三维温度场进行了瞬态模拟。(2)为了研究复杂生物组织在降温过程中,因温度梯度较大而导致热应力,采用ANSYS Workbench多物理场协同计算模块对肾脏组织的热应力进行了数值模拟。在计算模型中将肾脏组织、微毛细血管簇等视为多孔介质。在热结构耦合场计算中,将肾脏组织、动静脉血管壁视为固体介质,最后分析了不同灌注工况下,温度场与热应力的相关性。对肾脏器官冷灌注过程进行温度场、热应力场数值重构,目的在于探索冷激励作用下,温度以及降温速率耦合作用引起的生物力学效应,分析这种微小的热应力或热变形对细胞是否会造成物理损伤。(3)在冰温技术应用于器官延时保存的基础研究方面,分别测量了肾细胞悬液,肾器官的冰点温度等生物热物性参数。比较了不同保存温度对器官细胞活性的影响,冰温保存与目前临床应用的保存温度相比,降低了3-4℃。 本文提出的保存温度(-0.8℃),,可有效抑制组织细胞的基础代谢率,减少细胞的能量消耗,降低低温损伤引起的细胞凋亡。将所提出的保温方法及保存温度,施用于猪肾脏自体移植临床试验,取得了延时20小时以上的良好效果。 通过深层次研究冰温范围复杂生物组织宏微观热质传递的特性,将生物传热与生物医学两个学科中的基础研究关键问题结合在一起,实现了理论凝练和技术创新。
[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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