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目的 评价Tacrolimus(FK5 0 6 )和细胞毒性T淋巴相关抗原4免疫球蛋白(CTLA4Ig)转基因腺病毒(AdCTLA4Ig)在耐受诱导中的作用。方法 按照是否接受FK5 0 6处理、心脏移植后有无骨髓细胞输注(bonemarrowtransfusion ,BMT)、术后有无AdCTLA4Ig输注及移植心脏来源,将实验动物随机分为8组,观察各组心脏移植物的存活时间,于术后第30天测定其中4组的混合淋巴细胞反应的特异性和非特异性抑制率以及其中4组的异基因嵌合水平。结果 无处理对照组移植心脏存活时间为(6 .5±0 .5 5 )d ;AdCTLA4Ig单一处理组及联合BMT组移植心脏存活时间分别为(37.5±2 .88)d和(39.2±3.31)d ,与无处理组比较,差异有统计学意义(P <0 .0 5 ) ,当把FK5 0 6处理加入到上述2组的处理方案中时,移植心脏存活时间缩短(P <0 .0 5 )。术后30d混合淋巴细胞反应(MLR)结果显示,AdCTLA4Ig +BMT组和AdCTLA4Ig组的特异性抑制率明显高于FK5 0 6 +AdCTLA4Ig +BMT组和FK5 0 6+AdCTLA4Ig组(P <0 .0 5 ) ,而非特异性抑制率并没有差别。术后30d的异基因嵌合水平检测显示,BMT +AdCTLA4Ig组的胸腺和外周血嵌合水平高于AdlacZ腺病毒组、无处理对照组和AdCTLA4Ig组(P <0 .0 5 )。结论 在耐受诱导过程中,当FK5 0 6和AdCTLA4Ig联合应用时,前者会对后者的作用产?
Objective To evaluate the role of Tacrolimus (FK5 0 6) and cytotoxic T lymphoid associated antigen 4 (CTLA4Ig) transgenic adenovirus (AdCTLA4Ig) in induction of tolerance. Methods The experimental animals were randomly divided into 8 groups according to whether they were treated with FK5 0 6, bone marrow transplantation (BMT) after cardiac transplantation, whether or not AdCTLA4Ig was transfused and cardiac allografts after cardiac transplantation. The survival time of the three groups were measured. The specific and non-specific inhibition rates of mixed lymphocyte reaction in the four groups and the allogeneic chimeric levels in the four groups were measured on the 30th day after the operation. Results The cardiac allograft survival time of untreated control group was (6.5 ± 0.55) days. The survival time of cardiac transplant in AdCTLA4Ig single group and combined BMT group were (37.5 ± 2.88) d and (39.2 ± 3.31) days, respectively d, compared with the untreated group, the difference was statistically significant (P <0. 05), when the FK5 0 6 treatment was added to the above two groups of treatment options, the survival time of transplanted heart shortened (P <0 .0 5). The results of mixed lymphocyte reaction (MLR) at 30 days after operation showed that the specific inhibition rates of AdCTLA4Ig + BMT group and AdCTLA4Ig group were significantly higher than those of FK5 + 6 + AdCTLA4Ig + BMT group and FK5 + 6 + AdCTLA4Ig group (P <0.05 ), While there is no difference in non-specific inhibition rate. The level of chimerism in thymus and peripheral blood of BMT + AdCTLA4Ig group was higher than that of AdlacZ adenovirus group, untreated control group and AdCTLA4Ig group (P <0.05) at 30 days after operation. Conclusion In the induction of tolerance, when FK5 0 6 and AdCTLA4Ig combined application, the former will be the role of the latter?