维生素D衍生物联合供者骨髓细胞输注诱导异基因大鼠心脏移植免疫耐受  

Combined use of vitamin D-derived drug and DBMC to induce tolerance on heterotopic rat cardiac allograft

作　　者：陈江华[1] 姜睿[1] 何强[1] 祝恒成[1] 王惠萍[1] 金娟[1] 陈莹[1] 

机构地区：[1]浙江大学医学院附属第一医院肾脏移植中心,杭州310003

出　　处：《中华器官移植杂志》2004年第1期38-41,共4页Chinese Journal of Organ Transplantation

基　　金：浙江省自然科学基金优秀青年人才专项基金资助 (编号 :N2 9853)

摘　　要：目的　探讨同种异基因心脏移植后免疫耐受的诱导。方法　建立大鼠颈部异位心脏移植模型 ,按分组分别给予门静脉输注供者骨髓细胞 (DBMC) (B组 )、骨化三醇灌胃 (C组 )、输注DBMC及骨化三醇灌胃 (D组 )以及环孢素A(CsA)灌胃 (E组 )。观察移植心脏的存活时间及心肌组织病理改变 ,测定心肌组织中肿瘤坏死因子及细胞间粘附分子 1mRNA的表达以及血清钙、磷浓度 ,进行受者与供者及无关第三品系大鼠脾细胞混合淋巴细胞培养 (MLR)。结果　D组移植心脏的存活时间较其它各组显著延长 (P <0 .0 5 ) ;术后 7d ,C组、D组、E组受者脾细胞均能显著抑制供者及第三方无关供者脾细胞作为刺激细胞引起的MLR ;D组手术前后血磷、血钙浓度的差异无显著性 (P >0 .0 5 ) ;各组急性排斥反应的程度 ,D组最轻 ;D组肿瘤坏死因子及细胞间粘附分子 1mRNA的表达受到显著抑制 ,与对照组 (A组 )、B、C组比较 ,差异有显著性 (P <0 .0 5 )。结论　骨化三醇灌胃联合DBMC输注可显著延长移植心脏的存活时间 ,二者具有协同作用。Objective To explore the effects of 1,25-(OH) 2-D 3 in combined with DBMC to induce tolerance on heterotopic rat cardiac allografts.Methods After the establishment of a stable rat cervical heterotopic heart transplantation model, inbred male Wistar rat hearts were transplanted to male SD rats. The experimental rats were divided into the following groups: Group A served as experimental control group, group B receiving 1,25-(OH) 2-D 3 5000 ng/kg, group C being treated with 1×10 8 DBMC, group D being treated with 1×10 8 DBMC in combined with 1,25-(OH) 2-D 3 5000 ng/kg and group E being treated with CsA 10?mg/kg. The survival time of donor hearts was observed, meanwhile, the donor specific mixed lymphocyte reaction (MLR) and concentrations of TNF-alpha and ICAM-1 in grafts were measured. HE staining inspected all specimens of heart grafts.Results The mean graft survival time (days) in the groups A, B, C, D and E group was 7.2 ± 1.6 , 10.6 ± 2.3 , 12.4 ± 2.5 , 68.3 ± 9.9 and 17.5 ± 4.4 , respectively. The results showed there were significant differences in graft survival time between the group D and the other groups ( P < 0.05 ). Cytokine mRNA analysis in the grafts 8 days after operation revealed a clear suppression of TNF-alpha and ICAM-1 in the group D rats. The proliferation of anergic cells in the group C, group D and group E in the MLR were strongly inhibited on the day 7 after transplantation. The typical features of acute rejection were observed by pathological studies in the specimens of all groups. There were not any severe complications among all receptors.Conclusion 1,25-(OH) 2-D 3 in combined with DBMC has a synergistic effect and can achieve the best effects on the inducement of immunological tolerance and the improvement of graft survival.

关 键 词：维生素D衍生物 骨髓细胞 异基因移植 大鼠 心脏移植 免疫耐受 

分 类 号：R654.2[医药卫生—外科学] R392.4[医药卫生—临床医学]