Saat R E, de Bruin R W, Heineman E, Jeekel J, Marquet R L
Erasmus University, Laboratory for Experimental Surgery, Rotterdam, The Netherlands.
Gut. 1991 Jun;32(6):654-6. doi: 10.1136/gut.32.6.654.
Rejection and graft versus host disease are prominent features in small bowel allotransplantation in rats. Cyclosporine treatment of the recipient and irradiation of the donor were used to circumvent these phenomena in the WAG to brown Norway rat model. Irradiation of the donor with five or 10 Gy did prevent graft versus host disease but resulted in a more vigorous rejection of small bowel allografts in untreated recipients (mean (SEM) survival times of 11.5 (0.4) (n = 8) and 7.5 (0.9) (n = 11) days respectively, versus 16.6 (2.6) days (n = 17), p less than 0.01). Cyclosporine treatment of the recipient (25 mg/kg on days 0, 1, 2, 4, and 6 after transplantation) led to a mean (SEM) survival time of 38.3 (8.5) days (n = 10); 20% of the animals developed graft versus host disease. Combined with 5 Gy donor pretreatment, a similar survival was obtained without occurrence of graft versus host disease. However, cyclosporine treatment combined with 10 Gy led to a significant shortening of graft survival (23.1 (6.8) days, n = 9). These results suggest that although irradiation is very effective in preventing graft versus host disease, high dosages may accelerate rejection either by making the graft more vulnerable to rejection or by completely removing the immuno-suppressive effect of graft versus host disease.
排斥反应和移植物抗宿主病是大鼠小肠同种异体移植中的突出特征。在WAG大鼠至棕色挪威大鼠模型中，对受体进行环孢素治疗以及对供体进行照射，以规避这些现象。用5 Gy或10 Gy照射供体确实可预防移植物抗宿主病，但在未治疗的受体中会导致小肠同种异体移植物的排斥反应更强烈（平均（标准误）存活时间分别为11.5（0.4）天（n = 8）和7.5（0.9）天（n = 11），而对照组为16.6（2.6）天（n = 17），p<0.01）。对受体进行环孢素治疗（移植后第0、1、2、4和6天给予25 mg/kg），平均（标准误）存活时间为38.3（8.5）天（n = 10）；20%的动物发生了移植物抗宿主病。与5 Gy供体预处理联合使用时，可获得相似的存活时间且未发生移植物抗宿主病。然而，环孢素治疗与10 Gy联合使用会导致移植物存活时间显著缩短（23.1（6.8）天，n = 9）。这些结果表明，尽管照射在预防移植物抗宿主病方面非常有效，但高剂量可能会通过使移植物更容易被排斥或完全消除移植物抗宿主病的免疫抑制作用来加速排斥反应。
