他克莫司撤药诱发大鼠肝移植急性排斥反应的病理学观察与分析  

Dynamically Observed Histopathologic Changes of Acute Rejection in Rat Orthotopic Liver Transplantation Model after Tacrolimus Discontinued

作　　者：李铸[1] 李立[1] 冉江华[1] 张升宁[1] 刘静[1] 刘滇生[1] 李来邦[1] 陈娟[1] 

机构地区：[1]昆明市第一人民医院(昆明医学院附属甘美医院)肝胆胰一病区,昆明650011

出　　处：《中国普外基础与临床杂志》2010年第12期1253-1257,共5页Chinese Journal of Bases and Clinics In General Surgery

摘　　要：目的建立大鼠肝移植急性排斥反应动物模型,观察大鼠肝移植术后他克莫司撤药诱发受体急性排斥反应的肝脏动态病理学变化,为临床肝移植术后他克莫司停药或者用药不规律所致急性排斥反应的预测和评估提供理论依据。方法通过Kamada二袖套法,建立雄性DA大鼠至Lewis大鼠的原位肝移植模型60例。受体大鼠术前1 d和术后7 d内饲喂治疗剂量的他克莫司,之后半量递减至停药。分别于术后7、14、21及28 d处死部分受体大鼠,获取肝组织标本,观察受体大鼠肝脏大体和镜下的动态病理学改变,并进行排斥活动指数评分,同时观察受体大鼠的术后生存时间。结果受体大鼠术后7 d内由于受他克莫司的保护,肝脏未出现典型的急性排斥反应表现,至术后14 d由于他克莫司的减量及撤出,迅速发生肝脏的急性排斥反应,术后14、21及28 d排斥活动指数评分分别为(3.7±0.9)分(、6.3±0.9)分和(8.1±0.7)分。受体术后生存时间为(20.85±0.71)d,中位生存期为21 d。结论通过围手术期短期饲喂治疗剂量他克莫司并逐渐减量至撤药诱发肝移植大鼠急性排斥反应模型术后的急性排斥反应,动态观察该实验条件下排斥反应发生的时限和严重程度,对临床肝移植术后类似情况下所发生的急性排斥反应具有一定的预测价值和严重程度评估价值。Objective To observe the dynamic histopathologic changes of acute rejection in rat orthotopic liver transplantation（OLT） model after tacrolimus discontinued and provide some prediction and evaluation data for clinical acute rejection after liver transplantation.Methods Kamada two-cuff technique was used to establish 60 rat OLT model,and male DA rats,male Lewis rats were used as donors and recipients respectively.Therapeutic amount of tacrolimus（0.05 mg/kg,twice per day,continued for 8 d,1 d before operation and 7 d after operation,intragastric administrated） was administrated to recipients,then continuously half dose was decreased every day beginning from day 8 after operation and tacrolimus administration was stopped on day 13.Liver tissues were collected on day 7,14,21,and 28 after liver transplantation.Histopathologic changes and rejection activity index（RAI） of liver tissues were observed,survival time of recipients was calculated.Results Owing to protection effects of tacrolimus,liver tissues displayed no significant histopathologic changes of acute rejection in 7 d after OLT,while typical acute rejection histopathologic changes began to be observed on day 14 after OLT due to tacrolimus discontinuation.On day 14,21,and 28,RAI were 3.7±0.9,6.3±0.9,and 8.1±0.7 respectively.Survival time of recipients was（20.85±0.71） d with a median of 21 d.Conclusion Acute rejection could be induced in rat OLT model after tacrolimus discontinuation,and data collected from this model shows some extent of predictive value and assessment value for clinical liver acute rejection.

关 键 词：大鼠 动物模型 原位肝移植术 急性排斥反应 他克莫司 

分 类 号：R657.3[医药卫生—外科学]