CTLA4- Ig抗大鼠肝移植排斥反應及誘導免疫耐受的實驗研究_《中國普外基礎與臨床雜志》

作者：

四川大學華西醫院普外科（成都610041）;;
通訊作者：嚴律南;

關鍵詞：

細胞毒淋巴細胞抗原4免疫球蛋白肝移植大鼠排斥反應免疫耐受

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【摘要】目的建立大鼠原位肝移植（ROLT）急性排斥反應模型，探討細胞毒淋巴細胞抗原4免疫球蛋白（CTLA4Ig）抗排斥反應和誘導免疫耐受的作用。方法采用“二袖套管”法建立Wistar→SD大鼠配對組合的肝移植后排斥反應模型，并于術后第2天腹腔內一次性注射CTLA4Ig（75 μg/只大鼠），與未給藥的相同組合的排斥反應模型鼠對照研究，觀察移植術后7 d 2組動物的一般情況、肝功能變化、移植肝病理改變及血清TNFα水平的變化，同時觀察CTLA4Ig組動物術后4個月時的上述情況，以了解CTLA4Ig抗排斥及誘導免疫耐受的作用。結果 ①對照組動物于肝移植術后6～14 d內相繼死亡；移植肝出現明顯的排斥反應的病理改變征象。 ②CTLA4Ig組動物于術后7 d及4個月均未見明顯的排斥反應表現，移植肝無明顯的排斥反應的病理改變征象，血清TNFα、ALT、AST、TBIL及DBIL水平均明顯低于對照組（P＜0.05），TP及Alb水平則明顯高于對照組（P＜0.05）。

結論 CTLA4Ig有抗排斥反應及誘導免疫耐受功能的作用；血清TNFα水平作為觀察ROLT后排斥反應的指標，可能有一定的參考價值。

引用本文： 智星,嚴律南,楊培,向春華. CTLA4- Ig抗大鼠肝移植排斥反應及誘導免疫耐受的實驗研究. 中國普外基礎與臨床雜志, 2005, 12(6): 600-604. doi: 復制

1 Renna Molajoni E, Cinti P, Orlandini AM, et al. Contribution of the direct and indirect allorecognition pathway to the rejection of liver allografts [Ｊ]. Transplant Proc, 1998; 30(5)21382 RennaMolajoni E, Cinti P, Evangelista B, et al. Role of the indirect recognition pathway in the development of chronic liver allograft rejection [Ｊ]. Transplant Proc, 1998; 30(5)21403 Vierling JM. Immunology of acute and chronic hepatic allograft rejection [Ｊ]. Liver Transpl Surg, 1999; 5(4 Suppl 1)S14 Bretscher P. The twosignal model of lymphocyte activation twentyone years later [Ｊ]. Immunol Today, 1992; 13(2)745 Lafferty KJ. A few steps along the path to adult transplantation tolerance [Ｊ]. Transplant Proc, 1999; 31(1-2A)11S6 No authors listed. Banff schema for grading liver allograft rejection: an international consensus document [Ｊ]. Hepatology, 1997; 25(3)6587 Neumann UP, Fischer U, Schmitz V, et al. Longterm graft acceptance after rat liver allograft transplantation induced by application of CTLA4Ig and donor specific spleen cell administration [Ｊ]. Transplant Proc, 2002; 34(5)14008 Li W, Lu L, Wang Z, et al. CTLA4Ig inhibits rejection of mouse liver allografts from Flt3ligandtreated donors and is associated with increased lymphocyte apoptosis [Ｊ]. Transplant Proc, 2001; 33(1-2)2469 Lenschow DJ, Zeng Y, Thistlethwaite JR, et al. Longterm survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig [Ｊ]. Science, 1992; 257(5071)78910 Larsen CP, Elwood ET, Alexander DZ, et al. Longterm acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways [Ｊ]. Nature, 1996; 381(6581)43411 Kirk AD, Harlan DM, Armstrong NN, et al. CTLA4Ig and antiCD40 ligand prevent renal allograft rejection in primates [Ｊ]. Proc Natl Acad Sci USA, 1997; 94(16)878912 陳實. 器官移植研究的熱點與爭議問題 [A]. 見陳實主編. 移植學前沿 [M]. 武漢：湖北科學技術出版社， 20026~713 Platz KP, Mueller AR, Rossaint R, et al. Cytokine pattern during rejection and infection after liver transplantation——mprovements in postoperative monitoring? [Ｊ]. Transplantation, 19967; 62(10)144114 Moudgil A, Bagga A, Toyoda M, et al. Expression of gammaIFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients [Ｊ]. Clin Transplant, 1999; 13(2)20115 Paul LC. Surrogate biomarkers of longterm outcome after kidney transplantation [Ｊ]. Ann Transplant, 2000; 5(2)516 陳忠華. 移植免疫耐受 [A]. 見陳實主編. 移植免疫學 [M]. 武漢：湖北科學技術出版社， 1998298~31217 Owen RD. Immunogenetic consequences of vascular anastomoses between bovine twins [Ｊ]. Science, 1954; 102(2)400.

1. 1 Renna Molajoni E, Cinti P, Orlandini AM, et al. Contribution of the direct and indirect allorecognition pathway to the rejection of liver allografts [Ｊ]. Transplant Proc, 1998; 30(5)21382 RennaMolajoni E, Cinti P, Evangelista B, et al. Role of the indirect recognition pathway in the development of chronic liver allograft rejection [Ｊ]. Transplant Proc, 1998; 30(5)21403 Vierling JM. Immunology of acute and chronic hepatic allograft rejection [Ｊ]. Liver Transpl Surg, 1999; 5(4 Suppl 1)S14 Bretscher P. The twosignal model of lymphocyte activation twentyone years later [Ｊ]. Immunol Today, 1992; 13(2)745 Lafferty KJ. A few steps along the path to adult transplantation tolerance [Ｊ]. Transplant Proc, 1999; 31(1-2A)11S6 No authors listed. Banff schema for grading liver allograft rejection: an international consensus document [Ｊ]. Hepatology, 1997; 25(3)6587 Neumann UP, Fischer U, Schmitz V, et al. Longterm graft acceptance after rat liver allograft transplantation induced by application of CTLA4Ig and donor specific spleen cell administration [Ｊ]. Transplant Proc, 2002; 34(5)14008 Li W, Lu L, Wang Z, et al. CTLA4Ig inhibits rejection of mouse liver allografts from Flt3ligandtreated donors and is associated with increased lymphocyte apoptosis [Ｊ]. Transplant Proc, 2001; 33(1-2)2469 Lenschow DJ, Zeng Y, Thistlethwaite JR, et al. Longterm survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig [Ｊ]. Science, 1992; 257(5071)78910 Larsen CP, Elwood ET, Alexander DZ, et al. Longterm acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways [Ｊ]. Nature, 1996; 381(6581)43411 Kirk AD, Harlan DM, Armstrong NN, et al. CTLA4Ig and antiCD40 ligand prevent renal allograft rejection in primates [Ｊ]. Proc Natl Acad Sci USA, 1997; 94(16)878912 陳實. 器官移植研究的熱點與爭議問題 [A]. 見陳實主編. 移植學前沿 [M]. 武漢：湖北科學技術出版社， 20026~713 Platz KP, Mueller AR, Rossaint R, et al. Cytokine pattern during rejection and infection after liver transplantation——mprovements in postoperative monitoring? [Ｊ]. Transplantation, 19967; 62(10)144114 Moudgil A, Bagga A, Toyoda M, et al. Expression of gammaIFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients [Ｊ]. Clin Transplant, 1999; 13(2)20115 Paul LC. Surrogate biomarkers of longterm outcome after kidney transplantation [Ｊ]. Ann Transplant, 2000; 5(2)516 陳忠華. 移植免疫耐受 [A]. 見陳實主編. 移植免疫學 [M]. 武漢：湖北科學技術出版社， 1998298~31217 Owen RD. Immunogenetic consequences of vascular anastomoses between bovine twins [Ｊ]. Science, 1954; 102(2)400.

《中國普外基礎與臨床雜志》

CTLA4- Ig抗大鼠肝移植排斥反應及誘導免疫耐受的實驗研究

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《中國普外基礎與臨床雜志》

CTLA4- Ig抗大鼠肝移植排斥反應及誘導免疫耐受的實驗研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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