中文摘要：

目的探讨应用环孢素A（CsA）联合钴原卟啉（CoPP）预防小鼠异基因造血干细胞移植（allo—HSCT）后移植物抗宿主病（GVHD）的作用。方法以C57BL／6小鼠为供鼠，Balb／c小鼠为受鼠，分为4组：清髓性全身照射（TBI）组，受鼠TBI后经尾静脉注射磷酸盐缓冲液；常规异基因移植组（KS组），受鼠TBI后经尾静脉注射供鼠骨髓细胞与脾细胞的混合悬液（含骨髓细胞5X10。个和脾细胞5X10。个）；CsA组，受鼠HSCT后腹腔注射CsA；CsA联合CoPP干预组（联合组），受鼠HSCT后腹腔注射CsA和CoPP。观察受鼠存活情况，记录体重。获取受鼠肝脏、小肠和皮肤组织样本，观察GVHD的病理变化；行Masson染色，观察。肾组织纤维化；检测受鼠肾组织血红素氧合酶-1（HO-1）mRNA的表达。结果与BS组和CsA组相比较，联合组GVHD程度较轻，体重下降较少且恢复较快。移植后30d时BS组累积存活率为36．8％，联合组为69．6%，CsA组为53．5％，差异有统计学意义（P〈0．05）。联合组小鼠肝脏、小肠和皮肤组织可见细胞水肿、变性均较轻，坏死少见，炎症细胞浸润较少，其病理改变较BS组和CsA组轻。联合组几乎无肾间质小管纤维化，而CsA组则较明显。联合组HO-1mRNA表达高于BS组，CsA组HO-1mRNA表达低于前两组（P〈0．05）。结论CsA和CoPP联合应用可增强CsA抗GVHD效应，并可减轻CsA的不良反应，其机制可能与HO-1表达匕调有关。

英文摘要：

Objective To explore prevention of cyclosporine A （CsA） combined with Cobalt protoporphyrin （CoPP） against murine graft versus-host disease （GVHD） after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Methods C57BL/6 （H-2Kb） mice were used as donors and BALB/c （H-2Ka） mice as recipients, which were randomly divided into 4 groups. The mice in total body irradiation group （TBI group） were lethally irradiated and injected intravenously with PBS; The mice in Allo-HSCT group （BS group） were lethally irradiated and injected intravenously with bone marrow cells and spleen cells; The mice in CsA intervention group （CsA group） were injected with CsA intraperitoneally after allo-HSCT; The mice in CsA combine with CoPP intervention group （combination group） received both CsA and CoPP intraperitoneally after allo- HSCT. Recipients were monitored for condition, survival rate and weight. The liver, small intestine and skin in the recipients were gained and pathological changes of GVHD were assessed. The kidney was stained with Masson staining dye to observe the tissue fibrosis. The expression levels of renal HO-1 mRNA in the recipients were detected. Results In contrast to BS and CsA groups, GVHD degree in combination group was mild, with less reduction and quick recovery of weight. On the day 30 after HSCT, survival rate in BS group was 36. 8%, and that in combination group and CsA group was 69. 6% and 53.5%0 respectively （P〈0. 05）. In comparison with BS and CsA groups, pathological changes in combination group were mild, cellular edema and degeneration degree of the liver, small intestine and skin were slight, and few necrosis and infiltrated inflammatory cells were observed. Tubulointerstitial fibrosis hardly occurred in combination group, but it occurred in CsA group abundantly. As compared with BS group, the expression levels of HO-1 mRNA was increased in combination group, while decreased in CsA group （P〈0. 05）. Conclusion CsA combined with CoPP enhance