小鼠心脏移植急性抗体介导的排斥反应模型的建立和分析  

Establishment and analysis of mouse model of acute antibody-mediated rejection in heart transplantation

作　　者：廖涛[1] 杨哲 张燕楠 韩飞[1] 孙启全[1] Liao Tao;Yang Zhe;Zhang Yannan;Han Fei;Sun Qiquan(Department of Renal Transplantation,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院肾移植科,广州510630

出　　处：《器官移植》2020年第3期362-368,共7页Organ Transplantation

基　　金：国家自然科学基金(81800663,81770753);广东省基础与应用基础研究基金(2019A1515011942)。

摘　　要：目的建立小鼠心脏移植急性抗体介导的排斥反应(AMR)模型并分析其特点。方法建立小鼠皮肤移植和心脏移植模型。根据处理方法不同分为同系对照组、非致敏组、预致敏组和预致敏+环孢素组(每组供、受体各9只)。观察各组移植物存活时间、供体特异性抗体(DSA)水平和病理学表现,分析其排斥反应的特点。结果同系对照组小鼠心脏移植物在3个月观察期内均长期存活,非致敏组、预致敏组和预致敏+环孢素组心脏移植物存活时间分别为(7.0±0.7)d、(2.6±0.5)d和(5.0±0.7)d,组间比较差异均有统计学意义(均为P<0.01)。预致敏组在心脏移植术后3 d、预致敏+环孢素组在心脏移植术后5 d DSA水平均较基础值显著升高,差异均有统计学意义(P<0.05,P<0.01)。非致敏组病理学表现为心肌细胞破坏,形成间质炎,C4d少量沉积,CD3细胞大量浸润;预致敏组和预致敏+环孢素组病理学表现为心肌细胞破坏,形成毛细血管炎,C4d大量沉积,但是前者CD3细胞浸润多于后者。结论利用不同品系间小鼠皮肤移植和心脏移植的基础上加用环孢素可成功建立实用性强的小鼠心脏移植急性AMR模型,为后续AMR的发病机制和干预研究提供基础。Objective To establish a mouse model of acute antibody-mediated rejection(AMR)in heart transplantation and to analyze its characteristics.Methods Mouse models of heart transplantation and skin transplantation were established.According to different treatment methods,all animals were divided into the homologous control group,non-sensitized group,pre-sensitized group and pre-sensitized+ciclosporin group(9 donors and 9 recipients in each group).The graft survival time,donor-specific antibody(DSA)level and pathological manifestations of each group were observed,and the characteristics of rejection were analyzed.Results In the homologous control group,the cardiac grafts of the mice survived for a long period of time during the 3-month observation period.The survival time of the cardiac grafts in the non-sensitized group,pre-sensitized group and pre-sensitized+ciclosporin group was(7.0±0.7)d,(2.6±0.5)d and(5.0±0.7)d,respectively.The differences among the groups were statistically significant(all P<0.01).The DSA level in the pre-sensitized group was significantly elevated than the baseline level at 3 d after heart transplantation,and that in the pre-sensitized+ciclosporin group was remarkably up-regulated at 5 d after heart transplantation,the differences were statistically significant(P<0.05,P<0.01).The pathological manifestation of the non-sensitized group was the myocardial cell destruction,the formation of interstitial inflammation,mild C4 d deposition and a large amount of CD3 cell infiltration.The pathological manifestations of the pre-sensitized group and the pre-sensitized+ciclosporin group showed myocardial cell destruction,capillary inflammation and a large amount of C4 d deposition,whereas the amount of CD3 cell infiltration in the pre-sensitized group was more than that in the pre-sensitized+ciclosporin group.Conclusions The use of ciclosporin on the basis of heart transplantation and skin transplantation between different strains of mice can successfully establish a practical acute AMR model in mouse hea

关 键 词：抗体介导的排斥反应 细胞介导的排斥反应 心脏移植 动物模型 供体特异性抗体 C4D 环孢素 

分 类 号：R617[医药卫生—外科学] R392.4[医药卫生—临床医学]