• 四川大學華西醫(yī)院普外科(成都610041);;
  • 通訊作者: 嚴律南;

【摘要】目的 建立大鼠原位肝移植(ROLT)急性排斥反應(yīng)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(yīng)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(yīng)模型,并于術(shù)后第2天腹腔內(nèi)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(yīng)模型鼠對照研究,觀察移植術(shù)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(shù)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(jié)果 ①對照組動物于肝移植術(shù)后6~14 d內(nèi)相繼死亡; 移植肝出現(xiàn)明顯的排斥反應(yīng)的病理改變征象。 ②CTLA4Ig組動物于術(shù)后7 d及4個月均未見明顯的排斥反應(yīng)表現(xiàn),移植肝無明顯的排斥反應(yīng)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(jié)論 CTLA4Ig有抗排斥反應(yīng)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(yīng)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(yīng)及誘導免疫耐受的實驗研究. 中國普外基礎(chǔ)與臨床雜志, 2005, 12(6): 600-604. doi: 復制

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  1. 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(shù)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(shù)出版社, 1998298~31217 Owen RD. Immunogenetic consequences of vascular anastomoses between bovine twins [J]. Science, 1954; 102(2)400.