版纳微型猪近交系与人肝脏合成蛋白功能匹配研究

发布时间：2018-10-19 19:23

【摘要】：供器官严重短缺是当今移植界所面临的两大难题之一。猪到人异种移植无疑为解决器官短缺这一矛盾提供新的思路。近年随着免疫学机制及猪到人异种移植基础研究的不断深入和基因改造技术的不断改进,已证实猪与人免疫学差异和排斥反应有望得到攻克。但目前国际上有关猪与人脏器生理功能匹配性研究仍鲜有报道。肝脏不仅是机体最大的解毒器官,生物转化、代谢、分泌和排泄机体内、外源代谢产物及药物,清除机体有毒物质。还是机体最主要的生物合成器官,合成白蛋白、球蛋白,凝血、纤溶和抗凝等血浆中大部分蛋白质,执行着极其重要的生理功能。异种移植术后,供猪肝脏能否替代人肝脏执行常规生理合成功能,能否清除机体内、外源性代谢产物,能否代谢和排泄术后长期大量使用的免疫抑制剂、抗菌及抗病毒药物,都是异种移植能否最终走上临床必须回答的问题。本研究以版纳微型猪近交系(Banna Minipig Inbred Line,BMI)为研究对象,分别测定BMI和人常规肝脏功能及肝脏合成蛋白潜在功能,比较BMI与人肝脏分泌、代谢能力,肝脏合成蛋白含量和功能差异。结果显示:BMI血清总胆红素和直接胆红素水平仅为人1/5-1/3;肝脏酶学水平均较人高,门冬氨酸
[Abstract]:The serious shortage of donor organs is one of the two major problems facing the transplantation community. Pig to human xenotransplantation undoubtedly provides a new way to solve the problem of organ shortage. In recent years, with the development of immunological mechanism, basic research of porcine to human xenotransplantation and the improvement of genetic modification technology, it has been proved that immunological differences and rejection reactions between pigs and human beings are expected to be overcome. However, there are few reports on physiological function matching of pig and human viscera. The liver is not only the largest detoxification organ, but also the biotransformation, metabolism, secretion and excretion of the body, exogenous metabolites and drugs, and the elimination of toxic substances. It is also the most important biosynthesis organ, the most important protein in plasma, such as albumin, globulin, coagulation, fibrinolysis and anticoagulant. After xenotransplantation, can the donor pig liver perform routine physiological synthesis function instead of human liver, clear the body and exogenous metabolites, metabolize and excrete a large number of immunosuppressants, antibacterial and antiviral drugs used for a long time after xenotransplantation. These are the questions that must be answered whether the xenotransplantation can finally be applied to the clinic. In this study, Banna miniature pig inbred line (Banna Minipig Inbred Line,BMI was used to determine the liver function of BMI, human routine liver function and potential function of liver synthetic protein, and to compare the difference between BMI and human liver secretion, metabolic ability, content and function of liver synthetic protein. The results showed that the serum levels of total bilirubin and direct bilirubin in BMI were only 1 / 5 / 1 / 3 of human, the level of liver enzyme was higher than that of human.
【学位授予单位】：四川大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R341

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