【摘要】：供器官嚴(yán)重短缺是當(dāng)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(xué)機(jī)制及豬到人異種移植基礎(chǔ)研究的不斷深入和基因改造技術(shù)的不斷改進(jìn),已證實(shí)豬與人免疫學(xué)差異和排斥反應(yīng)有望得到攻克。但目前國際上有關(guān)豬與人臟器生理功能匹配性研究仍鮮有報(bào)道。 肝臟不僅是機(jī)體最大的解毒器官,生物轉(zhuǎn)化、代謝、分泌和排泄機(jī)體內(nèi)、外源代謝產(chǎn)物及藥物,清除機(jī)體有毒物質(zhì)。還是機(jī)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(zhì),執(zhí)行著極其重要的生理功能。異種移植術(shù)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(jī)體內(nèi)、外源性代謝產(chǎn)物,能否代謝和排泄術(shù)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(duì)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(jié)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(xué)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(xué)位授予單位】：四川大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2005
【分類號(hào)】：R341

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本文編號(hào)：2282129