口服耐受与免疫抑制药物对移植后移植物抗宿主病抑制作用比较  

Comparison of graft versus host disease inhibitory effects between oral tolerization and immunosupression agents following transplantation

作　　者：赵刚[1] 陈宝安[1] 丁家华[1] 顾炎[1] 王珏琼[1] 邓晓静[1] 吴亚男[1] 

机构地区：[1]东南大学附属中大医院血液科,江苏省南京市210009

出　　处：《中国组织工程研究与临床康复》2009年第49期9681-9686,共6页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：江苏省重点学科开放课题(k0613)~~

摘　　要：背景:移植物抗宿主病是导致异基因外周血造血干细胞移植失败的主要原因,口服耐受是研究治疗移植物抗宿主病的新模式。目的:探讨骨髓移植前供鼠经口服受鼠脾淋巴细胞诱导耐受是否能增加异基因骨髓移植后受鼠对供者移植物的免疫耐受,从而减轻移植物抗宿主病,并与目前常用于预防移植物抗宿主病的免疫抑制药物比较作用效果。设计、时间及地点:随机分组设计,对比观察,于2008-12在东南大学医学院中心实验室完成。材料:供鼠为雄性纯种近交系小鼠C57BL/6J(H-2b),受鼠为雌性纯种近交系小鼠BALB/c(H-2d)。方法:用主要组织相容性抗原完全不合的纯种近交系小鼠建立异基因骨髓移植/移植物抗宿主病动物模型,小鼠共分5组,分别给予不同的急性移植物抗宿主病预防方案:①口服耐受组:移植前口服受鼠脾淋巴细胞相当于10μg蛋白,隔天1次,共3次。②雷帕霉素组:1.5mg/(kg?d)灌胃,从移植后第1天(+1d)开始用药。③环孢素A+甲氨蝶呤组:环孢素A1.5mg/(kg?d)腹腔注射,从移植后+1d开始用药,当小鼠的胃肠功能逐渐恢复后,改为环孢素A5mg/(kg?d)灌胃,甲氨蝶呤0.4mg/(kg?d)腹腔注射,移植后+1,+3,+6,+11d用药。④空白对照组:移植后未用药。⑤辐照不移植组:照射后未予骨髓移植。主要观察指标:各组小鼠骨髓移植后移植物抗宿主病的出现情况及免疫耐受指标差异。结果:移植后小鼠出现典型的移植物抗宿主病症状,空白对照组小鼠死亡高峰在移植后第14～18天,死亡率接近100%。口服耐受组、雷帕霉素组和环孢素A+甲氨蝶呤组小鼠急性移植物抗宿主病症状明显减轻,平均生存时间较空白对照组显著延长(P<0.05);小鼠急性移植物抗宿主病病理表现减轻,口服耐受组病理变化少于其他各组;流式细胞仪监测CD4+/CD8+比值增加,CD4+CD25+细胞增加,口服耐受组增加明显;ELISA检测移植物抗宿主病产生相应细胞�BACKGROUND：The graft versus host disease （GVHD） is the main reason for allogeneic hematopeic stem cell transplantation （allo-HSCT） failure,and oral tolerization is a newly developed treating method.OBJECTIVE：To evaluate the inhibition effect of acute GVHD induced by feeding donors with recipient splenocytes orally before allo-HSCT in a murine model and to compare the immune tolerance with immunosupression agents currently used in clinical treatment.DESIGN,TIME AND SETTING：A randomized grouping design of contrast observation was performed at the Center Laboratory of School of Medicine,Southeast University in December 2008.MATERIALS：The male C57BL/6J（H-2b） mice were served as donors,and the female （BALB/C） mice （H-2d） were served as recipients.METHODS：The mice were prepared allo-HSCT/GVHD models,and divided into 5 groups,which received prevent scheme.① Oral tolerization group：C57BL/6J mice were fed with BALB/C （H-2d） splenocytes before the transplantation,with dose of 10 μg per time,1 day interval,for 3 times.②Rapamycin group：mice were intragastric administrated rapamycin from the 1st after transplantation with dose of 1.5 mg/（kg·d）.③Ciclosporin A＋ methotrexate group：mice were intragastric administrated ciclosporin A with 1.5 mg/（kg·d）,increased to 5 mg/（kg·d） when mice were recovered the gastrointestinal function,and received intragastric administrated 0.4 mg/（kg·d） methotrexate at days 1,3,6 and 11 after transplantation.④Blank control group：no medication after transplantation.⑤Irradiation group：mice were received no transplantation.MAIN OUTCOME MEASURES：The presence of GVHD after allo-HSCT,and the difference of immune tolerance index.RESULTS：Typical GVHD symptoms occurred in all mice after transplantation.In the blank control group,most mice dead at days 14-18 and the mortality was nearly 100%.Compared to the blank control group,the symptoms were significantly ameliorated and the median survival times were extended in the other 3 tra

关 键 词：口服耐受 过继转输 移植物抗宿主病 异基因骨髓移植 

分 类 号：R394.2[医药卫生—医学遗传学]