中文摘要：

目的：观察腺病毒介导融合基因细胞毒性T淋巴细胞相关抗原-4（cytotoxic T-lymphocyte associated antigen-4，CTLA-4Ig）局部转染大鼠同种异体移植的复合组织对急性排斥反应的抑制作用。方法：以近交系Brown Norway大鼠为供体，Lewis大鼠为受体，采用腹部游离皮瓣作为异体复合组织移植（composite tissue allotransplantation，CTA）模型。将受者分为3组，A组（空白对照组）：异体皮瓣离体保存时不感染腺病毒，只灌注PBS溶液；B组（阴性对照组）：异体皮瓣离体保存时灌注携带增强型绿色荧光蛋白的重组腺病毒（Ad—EGFP）；C组（基因治疗组）：异体皮瓣离体保存时灌注AdCTLA-4Ig。术后观察各组移植皮瓣的排斥情况及存活天数，进行组织病理学检查，并观察CTLA-4Ig在移植组织中的表达情况及对急性排斥反应的抑制作用。结果：①A组、B组皮瓣移植物平均生存时间分别为（7．8±1．5）天和（7．1±1．6）天，C组移植皮瓣平均存活时间为（10．4±2．3）天，C组存活期长于A组和B组，差异有统计学意义（P〈0．01）；②移植皮瓣病理学检查：术后第7天，A组与B组移植皮瓣均发生严重急性排斥反应，而C组排斥反应较A组和B组轻微，但C组术后第11天也表现出严重急性排斥反应；③移植前后血清白细胞介素2（interleukin-2，IL-2）水平：各组移植术后早期发生急性排斥反应时，IL-2均有明显升高，但实验组血清IL-2水平在第3天、第7天时均明显低于两对照组（P〈0．01）。结论：建立了一种新的异体复合组织移植局部基因转染模型，皮瓣灌注AdCTLA-4Ig能获得融合基因在移植复合组织中的表达，局部产生的CTLA-4Ig能抑制急性排斥反应的发生，延长移植物存活时间。

英文摘要：

Objective To observe the effect of gene transfer of CTLA-4Ig delivered by adenovirus to inhibit the acute rejection of composite tissue allograft （CTA） in rat. Methods The epigastric flaps from Brown Norway rats were transplanted into Lewis recipients to set up CTA model. 30 couples of rats were randomly devided into 3 groups： Group A, n=10, control, without treatment. Donor flap femoral artery was perfused ex vivo after harvest with PBS solution containing no adenovirus. Group B, n=10, AdEGFP was perfused into donor flap via femoral artery after flap harvest. Group C, n=10, treated with AdCTLA-41g. Observe the survive ratio of animal and rejection time of composite tissue flap, histologic outcomes, and the level of IL-2 of blood serum to evaluate the inhibition to acute rejection. Results The average survival times of flap grafts in group A and group B were （7.8 ± 1.5） days and （7.1 ± 1.6） days. In contrast, the survival time of group C was （10.4±2.3）days, which was longer than group A and group B, the difference was statistically significant （P〈0.01）. Histologic outcomes and the level of IL-2 were coincident with the acute rejection observed outside the flap. Conclusion Using ex vivo gene transfer technique, CTLA-4Ig gene can be introduced to the flap graft during physiological temperature preservation. The modified graft can express and excrete CTLA-4Ig locally, which can suppress acute alloimmune response and is responsible for prolongation of graft survival.