【摘要】 目的:建立大鼠原位肝脏移植的急性排斥模型并观察其排斥反应的特点.方法:采用近交系雄性DA大鼠为供体,Lewis大鼠为受体,改良“二袖套”法建立肝脏移植模型30例.随机分为两组,对照组(n=15)术后不用免疫抑制剂,FK506处理组(n=15)术后1~7d用FK5060.2mg/(kg·d)灌胃.术后4,7和10d分别随机处死3只,检测血清肝功能生化指标[天冬氨酸转氨酶(AST)、总胆红素(BILI)]以及肝脏病理组织学变化,每组各留6只观察生存期.结果:术后7和10d时对照组血清AST,BILI浓度均高于FK506处理组[AST:7d,(17.7±3.6)μkat/Lvs(7.9±1.6)μkat/L,P<0.05;10d,(21.9±4.3)μkat/Lvs(4.7±0.7)μkat/L,P<0.05.BILI:7d,(90.9±18.8)μmol/Lvs(6.8±0.7)μmol/L,P<0.05;10d,(111.5±23.3)μmol/Lvs(15.5±3.2)μmol/L,P<0.05].术后7d,对照组移植物出现明显的排斥反应的病理学变化,10d时更为严重.FK506组术后7和10d病理学检查为不明确或轻度的排斥表现.对照组中位生存时间为12d,95%可信区间为(11.77~13.90)d(n=6,12d×4,14d×1,15d×1).FK506处理组中位生存时间为78d,95%可信区间为(65.26~90.74)d(n=6,>65d×1,>67d×1,76d,78d,89d和90d),生存时间明显较对照组延长(P<0.05).结论:DA到Lewis大鼠品系组合可以建立稳定可靠的肝脏移植急性排斥模型;该模型的排斥反应的特点与临床相似,且可以为抗排斥药物FK506预防而达到长期存活.更多还原

【Abstract】 AIM: To establish an acute rejection model of DA-to-Lewis rat liver transplantation (LT) and observe the characteristics of acute rejection. METHODS: Thirty LT models were established by modified Kamada two-cuff technique, with inbred male DA rats as the donors and inbred male Lewis rats as the recipients. The recipients were randomly divided into 2 groups: control group (n=15) without immuno-suppressive agent treatment after LT and FK506 treatment group (n=15) lavaged with 0.2 mg/(kg·d) FK506 from 1 to 7 d after LT. Every 3 recipients were sacrificed respectively at day 4, 7, 10 after LT to detect the changes of serum biochemistry aspartate aminotransferase (AST) and total bilirubin (BILI) and the grafts histology. The other 6 recipients were left in each group to observe the animal survival time. RESULTS: The serum concentrations of AST and BILI in control group were higher than in FK506 treatment group at day 7 and 10 after LT AST: 7 d, (17.7±3.6) μkat/L vs (7.9± 1.6) μkat/L, P<0.05; 10 d, (21.9±4.3) μkat/L vs (4.7± 0.7) μkat/L, P<0.05. BILI: 7 d, (90.9±18.8) μmol/L vs (6.8±0.7) μmol/L, P<0.05; 10 d, (111.5± 23.3) μmol/L vs (15.5±3.2) μmol/L, P<0.05. In control group, the histological manifestations of the grafts were obvious rejection at day 7, and became more sever at day 10. In FK506 treatment group, the histological manifestations were mild or uncertain rejection at day 7 and 10. In control group, the median survival time was 12 d and the 95% confidence interval was (11.77 -13.90) d (n=6, 12 d×4, 14 d×1, 15 d×1). In FK506 treatment group, the median survival time was 78 d and the 95% confidence interval was (65.26-90.74) d (n=6, >65 d×1, >67 d×1, 76 d, 78 d, 89 d, 90 d). FK506 treatment group has the longer survival time than control group (P<0.05). CONCLUSION: DA-to-Lewis rat strain combination is a stable rejection model of rat liver transplantation. The features of this model are similar to the clinical rejection that can be reversed by immunosuppressive agent FK506.更多还原