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  本文選題：CTLA4-Ig　切入點(diǎn)：肝移植　出處：《中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院》2007年碩士論文　論文類型：學(xué)位論文

【摘要】： 目的：通過(guò)建立大鼠原位肝移植模型，探討CTLA4-Ig抗排斥反應(yīng)和誘導(dǎo)免疫耐受的作用。 方法：采用近交系雌性DA大鼠作供體、雌性LEW大鼠作受體，“二袖套法”建立肝臟移植模型20例。術(shù)前隨機(jī)分為2組：A組即排斥組(DA→LEW，n=10)，只進(jìn)行原位肝移植；B組即CTLA4-Ig基因治療組(DA→LEW，n=10)，在供肝冷保存時(shí)，將CTLA4-Ig基因?qū)氪笫笠浦哺�。A、B兩組受體分別于術(shù)后3、7、16d經(jīng)眼球取血獲得血清標(biāo)本。術(shù)后7d各組隨即處死2例，收集肝臟標(biāo)本。血清標(biāo)本檢測(cè)IL-2、ALT、AST、TBIL的濃度。肝臟標(biāo)本觀察移植物病理學(xué)變化。 結(jié)果：成功建立了大鼠原位肝移植模型。DA→LEW近交系大鼠肝移植后移植排斥反應(yīng)強(qiáng)烈，在不使用免疫抑制劑的情況下，生存時(shí)間＜14天，是進(jìn)行肝移植免疫研究的可靠模型。術(shù)前大鼠血清IL-2濃度362.31±49.26 ng／L。肝移植術(shù)后，IL-2的濃度在A組中升高到較高水平，而在B組中則維持一個(gè)較低的水平。術(shù)后3、7d，A組與B組血清IL-2的濃度存在非常顯著的差異。術(shù)前、術(shù)后3d，A組與B組ALT、AST、TBIL之間無(wú)統(tǒng)計(jì)學(xué)差異；術(shù)后7d，A組濃度明顯高于B組(P＜0.05)。A組與B組，在術(shù)后7d行移植肝取材，病理學(xué)證實(shí)：A組移植肝發(fā)生嚴(yán)重的細(xì)胞性排斥，B組可見(jiàn)移植肝組織損傷程度輕。 結(jié)論：在DA→LEW大鼠原位肝移植的基礎(chǔ)上，，于供肝冷保存時(shí)應(yīng)用腺病毒載體介導(dǎo)CTLA4-Ig基因轉(zhuǎn)染供肝，可以抑制同種異體免疫反應(yīng)，在不使用常規(guī)免疫抑制劑的情況下，能延長(zhǎng)移植肝的存活時(shí)間，降低受體對(duì)供體移植物的免疫反應(yīng)性。
[Abstract]:Aim: to establish an orthotopic liver transplantation (OLT) model in rats to investigate the effects of CTLA4-Ig on anti rejection and immune tolerance. Methods: twenty cases of liver transplantation model were established by using inbred female DA rats as donor and female LEW rats as recipients. Before operation, 20 cases of liver transplantation were randomly divided into two groups: group A: rejection group. 鈫扡EWN 10, orthotopic liver transplantation group B (CTLA4-Ig gene therapy group). 鈫扺hen the donor liver was cryopreserved, the CTLA4-Ig gene was introduced into the transplanted liver of rats. The blood samples were collected from the eyeball on the 7th and 16th day after operation, and 2 patients in each group were killed 7 days after operation. Liver samples were collected. Serum samples were collected to detect the concentration of IL-2ALT TBIL. Liver specimens were observed for the histopathological changes of grafts. Results: the rat orthotopic liver transplantation model was successfully established. DA. 鈫扵he rejection of LEW inbred rats after liver transplantation was strong, and the survival time was less than 14 days without the use of immunosuppressants. The serum IL-2 concentration of rats before operation was 362.31 鹵49.26 ng / L. The level of IL-2 increased to a higher level in group A after liver transplantation. There was significant difference in serum IL-2 concentration between group A and group B. there was no significant difference between group A and group B 3 days after operation, and the concentration of serum IL-2 in group A was significantly higher than that in group B at 7 days after operation (P < 0.05), but there was no significant difference between group B and group A on the 3rd day after operation (P < 0.05), but there was no significant difference between group A and group B on the 7th day after operation (P < 0.05), but there was no significant difference between group B and group A on the 3rd day after operation (P < 0.05). The grafts were taken on the 7th day after operation. The pathological evidence showed that the grafts in group A had severe cellular rejection and that the grafts in group B had slight liver tissue damage. Conclusion: in DA. 鈫扥n the basis of orthotopic liver transplantation (OLT) of LEW rats, CTLA4-Ig gene transfection mediated by adenovirus vector during cold preservation of donor liver could inhibit the allogeneic immune response without routine immunosuppressive agents. It can prolong the survival time of the transplanted liver and decrease the immunoreactivity of the recipient to the donor graft.
【學(xué)位授予單位】：中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2007
【分類號(hào)】：R657.3;R392

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 吳劍英，徐冠南，呂隨峰，王孟龍，傅志仁，王元和;150例大鼠原位肝移植手術(shù)方法比較[J];第二軍醫(yī)大學(xué)學(xué)報(bào);1996年03期

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