版納微型豬近交系與人肝臟合成蛋白功能匹配研究
發(fā)布時間:2018-10-19 19:23
【摘要】:供器官嚴重短缺是當今移植界所面臨的兩大難題之一。豬到人異種移植無疑為解決器官短缺這一矛盾提供新的思路。近年隨著免疫學機制及豬到人異種移植基礎研究的不斷深入和基因改造技術的不斷改進,已證實豬與人免疫學差異和排斥反應有望得到攻克。但目前國際上有關豬與人臟器生理功能匹配性研究仍鮮有報道。 肝臟不僅是機體最大的解毒器官,生物轉化、代謝、分泌和排泄機體內、外源代謝產物及藥物,清除機體有毒物質。還是機體最主要的生物合成器官,合成白蛋白、球蛋白,凝血、纖溶和抗凝等血漿中大部分蛋白質,執(zhí)行著極其重要的生理功能。異種移植術后,供豬肝臟能否替代人肝臟執(zhí)行常規(guī)生理合成功能,能否清除機體內、外源性代謝產物,能否代謝和排泄術后長期大量使用的免疫抑制劑、抗菌及抗病毒藥物,都是異種移植能否最終走上臨床必須回答的問題。本研究以版納微型豬近交系(Banna Minipig Inbred Line,BMI)為研究對象,分別測定BMI和人常規(guī)肝臟功能及肝臟合成蛋白潛在功能,比較BMI與人肝臟分泌、代謝能力,肝臟合成蛋白含量和功能差異。結果顯示:BMI血清總膽紅素和直接膽紅素水平僅為人1/5-1/3;肝臟酶學水平均較人高,門冬氨酸
[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.
【學位授予單位】:四川大學
【學位級別】:博士
【學位授予年份】:2005
【分類號】:R341
本文編號:2282129
[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.
【學位授予單位】:四川大學
【學位級別】:博士
【學位授予年份】:2005
【分類號】:R341
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