Oberhuber G, Schmid T, Erdkönig R, Thaler W, Ofner D, Köröszi G, Klima G, Margreiter R
Department of Pathology, University of Innsbruck, Austria.
Eur Surg Res. 1991;23(3-4):206-13. doi: 10.1159/000129154.
The effect of ciclosporin (CS) and methotrexate (MTX) on the development of graft-versus-host (GvH) disease was examined after small bowel allotransplantation in the rat. The drugs were tested either alone or in combination. Lewis small bowel allografts were transplantated into Brown Norway recipients in a heterotopic position. The native small bowel, spleen, liver, skin, mesenteric lymph nodes and the kidney of the recipients were examined histologically 5, 10 and 20 days after allotransplantation. Intraepithelial lymphocyte numbers were determined quantitatively in the native small bowel. The relative spleen weight of the host was determined after sacrifice for estimation of the severity of GvH disease. Grade I GvH reaction of the native small bowel occurred in the animals without immunosuppression, but graft rejection predominated in this group. Treatment with CS was effective in the early postoperative periods; after 10 and 20 days GvH lesions in the native small bowel were comparable to those observed in the allogeneic combinations. MTX had a detrimental effect on the allografts and the GvH reaction was augmented. When CS and MTX were combined, GvH lesions were comparable to those in the animals treated solely with CS. Animals, however, suffered from heavy side effects. The spleen, liver, lymph nodes and kidney exhibited only unspecific histologic changes, which could not unequivocally be recognized as a GvH reaction. This was true for all groups. As a conclusion it can be said that GvH reaction occurs in the early postoperative period in a fully allogeneic model and cannot be prevented by CS in the dosae used. MTX was not seen to be of any value in this regard.
在大鼠小肠同种异体移植后，研究了环孢素（CS）和甲氨蝶呤（MTX）对移植物抗宿主（GvH）病发展的影响。单独或联合测试了这些药物。将Lewis小肠同种异体移植物异位移植到Brown Norway受体中。在同种异体移植后5、10和20天，对受体的天然小肠、脾脏、肝脏、皮肤、肠系膜淋巴结和肾脏进行组织学检查。定量测定天然小肠中的上皮内淋巴细胞数量。处死动物后测定宿主的相对脾脏重量，以评估GvH病的严重程度。在未进行免疫抑制的动物中，天然小肠出现了I级GvH反应，但该组中移植排斥反应占主导。CS治疗在术后早期有效；10天和20天后，天然小肠中的GvH病变与在同种异体组合中观察到的病变相当。MTX对同种异体移植物有不利影响，GvH反应增强。当CS和MTX联合使用时，GvH病变与仅用CS治疗的动物中的病变相当。然而，动物出现了严重的副作用。脾脏、肝脏、淋巴结和肾脏仅表现出非特异性组织学变化，无法明确认定为GvH反应。所有组均如此。可以得出结论，在完全同种异体模型中，GvH反应在术后早期发生，并且在所使用的剂量下，CS无法预防。在这方面，MTX没有任何价值。
