Small intestine transplantation in the rat--immunology and function.
Small intestine transplantation in the rat--immunology and function.
复制标题
大鼠小肠移植——免疫学和功能。
作者：
Kirkman Rl;Lear Pa;Madara Jl;N. Tilney
在大鼠近交系中进行异位、带血管的小肠移植，研究环孢素（CyA）免疫抑制和不免疫抑制对小肠移植的结构、功能和免疫影响。未处理的Lewis受体在7 ~ 10天后产生Lewis X Brown Norway F1肠排斥反应。在结构上，排斥肠的特征是隐窝缩短，绒毛内衬受损的减薄上皮细胞。在功能上，排斥反应与上皮活性离子转运受损有关，这可以通过电位差的降低来体现；排斥反应与上皮屏障功能的减弱有关，这可以通过上皮阻力的降低来体现。给予CyA 7 d可预防临床排斥反应，部分预防结构和功能缺陷。Lewis肠移植到Lewis X Brown Norway F1受体后，在9 ~ 17天内引起致死性移植物抗宿主病（GVHD）。CyA治疗7天不能常规预防GVHD，但延长给药时间延迟致命性GVHD，直到停用CyA。Lewis“B”大鼠的肠道通过胸腺切除、照射和同源T细胞耗尽的骨髓重建来缺乏T细胞，但未能引起Lewis受体的GVHD。移植前用T细胞重建的“B”大鼠恢复了GVHD反应。这些结果可能与临床小肠移植的考虑有关。
Heterotopic, vascularized small intestine transplants were performed in inbred strains of rats to investigate the structural, functional, and immunologic consequences of intestinal transplantation with and without immunosuppression with cyclosporine (CyA). Lewis X Brown Norway F1 intestine was rejected by untreated Lewis recipients in 7 to 10 days. Structurally, rejected intestine was characterized by shortened crypts and villi lined by damaged attenuated epithelial cells. Functionally, rejection was associated with impaired epithelial active ion transport as indicated by decreased potential difference and with diminished epithelial barrier function as reflected by decreased transepithelial resistance. Administration of CyA for 7 days prevented clinical rejection and partially prevented the structural and functional defects. Lewis intestine transplanted into Lewis X Brown Norway F1 recipients caused fatal graft versus host disease (GVHD) in 9 to 17 days. Treatment with CyA for 7 days failed to prevent GVHD routinely, but prolonged administration delayed fatal GVHD until CyA was discontinued. Intestine from Lewis "B" rats made deficient of T cells by thymectomy, irradiation, and reconstitution with syngeneic T cell-depleted bone marrow failed to cause GVHD in Lewis recipients. Reconstitution of the "B" rats with T cells before transplantation restored the GVHD response. These results may be relevant in the consideration of clinical small intestinal transplantation.