普乐可复在异种小肠移植中的作用

Effect of immunosuppressant FK506 on syrian hamster to rat small bowel xenotransplantation

目的探讨免疫抑制剂普乐可复(FK506)对于异种小肠移植后迟发异种移植物排斥反应和细胞介导的异种移植物排斥反应的作用。方法采用仓鼠-大鼠动物实验模型,分为对照组和治疗组。治疗1组为单纯用FK506组;治疗2组为FK506加脾切除组。观察移植肠管吸收功能、体重、生存时间、FK506血药浓度及移植肠管苏木精-伊红染色。结果治疗1、2组的生存时间分别为(29.5±2.4)d和(106.6±26.3)d,与对照组(4.3±0.5)d相比显著延长(P<0.01);且治疗1、2组之间相比,差异亦有非常显著性意义(P=0.006)。术后第4d对照组苏木精-伊红染色可见绒毛萎缩,有大量炎性细胞浸润。治疗组小肠黏膜显示高分泌状态。术后126d治疗2组小肠肌层明显增厚、绒毛萎缩、肠壁小动脉壁纤维化。结论FK506可抑制异种小肠移植后迟发异种移植物排斥反应和细胞介导的异种移植物排斥反应;加脾切除可明显延长异种小肠移植的存活时间;但不能逆转异种小肠移植后所发生的慢性排斥反应。

Objective To investigate the inhibition role of immunosuppressant FK506 on delayed xenografts rejection and cell mediated xenografts rejection in xenogeneic intestinal model of hamster to rat. Methods Syrian hamster and Wister rat were used as donors and recipient respectively. The recipient received FK506 treatment and FK506 plus splenectomy. FK506 (2 mg·kg-1·d-1)was given by intramuscular injection at 1 hour before operation and once everyday from 1 to 10 days after operation, then every 2 days until 60 days after operation. Survival time of grafts, body weight, absorbent function of transplanted intestine, concentration of FK506 and histological morphology of grafts were observed. Results Survival times of FK506 group and FK506 plus splenectomy group were(29.5±2.4)d and(106.6±26.3)d respectively, significantly longer than that of the control group [(4.3±0.5)d] (P< 0.01). There was significant difference in survival time between the FK506 group and FK506 plus splenectomy group (P=0.006). Weight of rats decreased obviously and increased again slowly after transplantation. Histological staining revealed villus atrophy and inflammatory cell infiltration in the control group, but villus proliferation, fewer inflammatory cells and high secretion status in the treatment groups. Conclusions FK506 can inhibit delayed xenografts rejection and cell mediated xenografts rejection. FK506 plus splenectomy can significantly prolong survival time of xenografts, but FK506 can not reverse chronic rejection after xenotransplantation.