供体骨髓输注减轻同种肝移植排斥反应  

Infusion of donor specific bone marrow alleviates acute rejection reaction in liver allotransplantation

作　　者：谢海洋[1] 贾长库[1] 郑树森[1] 

机构地区：[1]浙江大学医学院附属第一医院外科研究所卫生部多器官联合移植研究重点实验室,浙江杭州310003

出　　处：《中国病理生理杂志》2006年第11期2173-2176,共4页Chinese Journal of Pathophysiology

基　　金：国家重点基础研究项目资助(973项目;No.2003CB515501)

摘　　要：目的:研究非清髓性骨髓移植在同种肝移植免疫反应中的作用及其意义。方法:动物实验为同种大鼠肝移植:Ⅰ组为W istar→W istar同基因对照组;Ⅱ组为SD→W istar急性排斥组;Ⅲ组为SD→W istar环孢素A(cy-c losporine A,CsA)肌肉注射处理组;Ⅳ组为SD→W istar术前1周大剂量供体骨髓细胞输注处理组。用术后一般状态、生存时间、病理学排斥分级、肝标本中IL-2、IFN-γ的表达以及胸腺内嵌合体的检测等手段,确定不同处理组移植后的排斥反应情况及机体的免疫状态。结果:Ⅰ组大鼠术后无排斥反应发生;Ⅱ组大鼠术后9-13 d内全部死亡,中位存活时间(10.7±0.5)d,排斥反应明显;Ⅲ组大鼠仅见轻度排斥;Ⅳ组自然存活亚组6只大鼠4只长期存活(>100 d),排斥分级明显低于Ⅱ组(P<0.05),与Ⅱ组相比,Ⅳ组IL-2、IFN-γ蛋白的表达均明显下调。在骨髓输注15 d后,用PCR法在雌性W istar大鼠受体胸腺内可检测到雄性SD大鼠供体特异性的Y染色体(Y-chromosom e-spec ific sequence,Sry)基因片段。结论:供体骨髓输注可形成供受体细胞的嵌合状态,可降低同种异体肝移植的排斥反应,延长受体生存时间。AIM： To study the effect of nonmyeloablative donor specific bone marrow infusion on the immunoreaction of liver allotransplantation and its implication. METHODS： Orthotopic liver transplantation model was used in this study. Groups were set up as follows ： Group Ⅰ, syngeneic control （ Wistar - to - Wistar） ; Group Ⅱ, acute rejection （ SD - to -Wistar） ; Group Ⅲ, acute rejection treated with cyclosporine A by intramuscular injection （SD- to- Wistar ＋ CsA）. Group Ⅳ, bone marrow infusion 7 d before transplantation. General characteristics and survival time were observed. Histological grades of rejection were determined by pathological examination. IL - 2 and IFN -γ, expression in grafted liver were detected by Western blotting. Chimerism of donor cells was also measured by PCR for a male - specific marker （ Y - chromosome -specific sequence, Sry）. RESULTS： No signs of rejection were found in Group Ⅰ. Acute rejection occurred in group Ⅱ , and all the recipients died 9 - 13 d posttransplantation with median survival time being （ 10. 7 ± 0. 5 ）d. Only mild rejection was seen in group Ⅲ. As for group Ⅳ, 4 out of 6 recipients had long - term survival （ 〉 100 d）, and the histological grade of rejection was significantly lower than that in group Ⅱ （ P 〈 0. 05 ）. Compared with group Ⅱ , the transcription level of IFN - α and IL - 2 markedly decreased in group Ⅳ. Y - chromosome - specific sequence （Sry） of male SD rats was detected in the bone marrow of female recipients at 15 d after bone marrow infusion. CONCLUSION： Donor specific bone marrow infusion enhances chimerism formation in bone marrow, alleviates the rejection of liver allotransplantation and improve survival of liver allotransplantation.

关 键 词：肝移植 移植物排斥 骨髓细胞 移植嵌合体 

分 类 号：R363[医药卫生—病理学]