灵长类动物ABO血型不合肾移植后超急性排斥反应模型的建立  

Establishment of a hyperacute rejection model in ABO-incompatible renal allotransplantation in non-human primates

作　　者：王军祥[1] 钟山[1] 王筱啸[1] 陈松[1] 陈实[1] 陈刚[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所 教育部/卫生和计划生育委员会器官移植重点实验室,武汉430030

出　　处：《中华器官移植杂志》2014年第7期421-425,共5页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金（30872384）

摘　　要：目的 建立灵长类动物ABO血型不合肾移植后超急性排斥反应模型.方法 选择B型血食蟹猴为受者,A型血食蟹猴为供者,行ABO血型不合同种肾移植.根据是否接受致敏预处理,将受者猴分为2组：（1）未致敏对照组（n=1）,直接施行血型不合的同种肾移植术;（2）KLH-A预致敏组（n=3）,预先皮下注射钥孔戚血蓝蛋白（KLH）偶联血型抗原A（KLH-A抗原）,致敏2周后施行血型不合的同种肾移植术.检测受者猴血清抗A血型抗体水平的变化,观察两组受者猴在移植术中开放血流1h内及术后移植肾存活情况,并对移植肾进行病理学检测及诊断.结果 在术中未观察到未致敏对照组移植肾超急性排斥反应的发生,术后存活超过30 d（血肌酐为263 μmol/L）;KLH-A预致敏组3例受者猴在致敏后14 d,血清中抗A抗体水平显著升高,肾移植术中血流开放1h内移植物即转为紫黑色,HE染色及免疫荧光检测证实均发生超急性排斥反应.结论 通过KLH偶联血型抗原预先致敏,以显著升高受者猴相应血型抗体水平的策略,能成功建立灵长类动物ABO血型不合肾移植超急性排斥反应模型.Objective To establish a hyperacute rejection model in ABO-incompatible renal allotransplantation in nonhuman primates.Method ABO-incompatible renal transplantation was performed using blood group B cynomolgus monkeys as recipients and blood group A cynomolgus monkeys as donors.The transplants were distributed into 2 groups according to whether the recipient monkey was presensitized or not：（1） non-presensitized control group （n =1）,not receiving any pretreatment; （2） KLH-conjugated blood group antigen A （KLH-A） presensitized group （n =3）,being presensitized by subcutaneous injection of KLH-A 2 weeks prior to ABO-incompatible renal transplantation.The serum anti-blood group A antibody levels were measured using a FACS method.The graft survival time was observed and the pathologic studies were performed using the endpoint renal graft tissue samples.Result In non-presensitized control group,no hperacute rejection was observed during the surgery.With the traditional CsA triple therapy,the renal allograft survived was more than 30 days without obvious rejection,and the serum creatinine level was 263 μmol/L at day 30.After the presentization with KLH-A,recipient monkeys of KLH-A presensitized group had a markedly increased anti-A antibody levels and rapidly rejected the renal allografts from blood group A donors within 1 h after the reperfusion,which was demonstrated to be a hyperacute rejection with the pathologic studies.Conclusion The strategy of presensitization with KLH-conjugated blood group antigen significantly increases the corresponding blood group antibodies and allows the establishment of a hyperacute rejection model in ABO-incompatible renal allotransplantation in nonhuman primates.

关 键 词：ABO血型不合 肾移植 超急性排斥反应 灵长类动物 

分 类 号：R457.11[医药卫生—治疗学] R699.2[医药卫生—临床医学]