术中输注供体脾细胞联合术后延迟使用小剂量他克莫司诱导同种异基因大鼠心脏移植免疫耐受  

Donor specific transfusion of splenocytes combined with delayed low dosage tacrolimus administration induce immune tolerance in allogene rat heart transplantation

作　　者：李剑锋[1] 鄢业鸿[1] 邹循锋[2] 谢青松[1] 张晓伟[1] 王共先[1] 

机构地区：[1]南昌大学第一附属医院器官移植科,330006 [2]德国埃森大学医学院生化科

出　　处：《器官移植》2011年第4期223-228,共6页Organ Transplantation

基　　金：江西省卫生厅科技计划(20051057)

摘　　要：目的观察移植术中经受体门静脉输注供体特异性脾细胞联合术后延迟使用小剂量他克莫司(FK506)对诱导大鼠同种心脏移植免疫耐受的作用。方法将Wistar大鼠和SD大鼠分为7组,A组至F组分别采用Wistar大鼠和SD大鼠作为供、受体,G组为SD→SD大鼠同基因移植对照。其中A组无任何处理,B组输注供体特异性脾细胞,C组与D组分别早期应用和延迟应用FK506[0.5 mg/(kg.d)],E组与F组既术中经门静脉输注供体脾细胞,又分别早期或延迟应用FK506。采用改良大鼠腹腔异位心脏移植。观察期为术后100 d,观察移植心存活时间及其病理变化。结果 G组移植心均长期存活(100 d)。A^F组存活时间分别为(7.4±0.9)d、(22.1±3.6)d、(8.0±0.8)d、(7.9±1.3)d、(24.4±4.5)d、(95.5±6.0)d。F组7/8移植心长期存活。C组、D组的移植心存活时间与A组比较差异无统计学意义(均为P>0.05)。与A组比较,B组、E组与F组的移植心存活时间明显延长(P<0.05~P<0.01)。而F组移植心存活时间又明显长于B组与E组。病理检查G组移植心心肌未见排斥反应。A组移植心术后9 d表现为3~4级排斥反应,F组存活时间达100 d的大鼠移植心未见排斥反应。结论术中经受体门静脉输注供体脾细胞联合延迟使用小剂量FK506使同种异基因大鼠在移植后早期免疫系统激活后再被抑制,有利于诱导同种移植免疫耐受。Objective To observe the effects of donor specific transfusion of splenocytes combined with delayed low dose tacrolimus（FK506）administration on the induction of immune tolerance in allogene rat heart transplantation.Methods Wistar rats and SD rats were divided into 7 groups.In A-F groups,Wistar and SD rats were respectively chosen as donors and recipients.And the G group was selected as homogenic control group,in which both the donors and recipients were SD rats.No treatment was done in A group.Donor specific splenocytes were transfused to recipients in B group.FK506[0.5 mg/（kg·d）] was respectively used in early or late time after transplantation in C and D groups.Donor specific splenocytes were transfused to recipients via portal vein in E and F groups.And FK506 was respectively used post-transplantation in early or late time in E and F groups.The improved celiac heterotopic rat heart transplantation was performed.The survival time and pathologic changes of transplanted heart were observed after transplantation.Results The transplanted hearts survived for a long time in G group（100 d）.The survival time of A-F groups were（7.4±0.9）d,（22.1±3.6）d,（8.0±0.8）d,（7.9±1.3）d,（24.4±4.5）d,（95.5±6.0）d respectively.Seven eighths of transplanted hearts survived for a long time in F group.There was no significant difference in survival time of transplanted hearts between C,D group and A group（all in P〈0.05）.Compared with A group,survival time of transplanted hearts was significantly longer in B,E and F group（P〈0.05-P〈0.01）.And survival time of transplanted hearts in F group was significantly longer than that in B and E group.The pathological examination showed no rejection appearance in the cardiac muscle of transplanted heart in G group.The transplanted hearts in A group stopped beating at 9 d after transplantation and pathological examination showed Grade 3-4 rejection.And no rejection was observed in the rats which survived for 100 days in F group.Conclusions Transfusio

关 键 词：心脏移植 脾细胞输注 他克莫司 免疫耐受 

分 类 号：R392.4[医药卫生—免疫学]