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Effect of local CTLA4Ig gene transfection on acute rejection of small bowel allografts in rats

机译:CTLA4Ig基因局部转染对大鼠小肠移植急性排斥反应的影响

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AIM: To evaluate the local expression of CTLA4Ig gene in small bowels and its effect on preventing acute rejection of the small bowel allografts. METHODS: Groups of Wistar rats underwent heterotopic small bowel transplantation from SD rats. The recipients were randomly divided into experimental group (allografts were transfected with CTLA4Ig gene) and control group (non CTLA4Ig gene transfected). In the experimental group, the donor small bowels were perfused ex vivo with CTLA4Ig cDNA packaged with lipofectin vector via intra-superior mesenteric artery before transplantation, and the CTLA4Ig expression in the small bowel grafts post-transplantation was assessed by immunohistology. On d 3, 7 and 10 post-transplantation, the allografts in each group were harvested for the examination of histology and detection of apoptosis. RESULTS: Small bowel allografts treated with CTLA4Ig cDNA showed abundant CTLA4Ig expression after transplantation. Acute rejection of grade Ⅰ on d 7 and grade Ⅱ on d 10 after transplantation was noticed in the control allografts, and a dramatically increased number of apoptotic enterocytes in parallel to the progressive rejection could be recognized. In contrast, the allografts treated with CTLA4Ig cDNA showed nonspecific histological changes and only a few apoptotic enterocytes were found after transplantation. CONCLUSION: Local CTLA4Ig gene transfection of small bowel allograft is feasible, and the local CTLA4Ig expression in the allograft can prevent acute rejection after transplantation.
机译:目的:探讨CTLA4Ig基因在小肠中的局部表达及其在防止小肠同种异体移植急性排斥反应中的作用。方法:Wistar大鼠组进行SD大鼠异位小肠移植。将受体随机分为实验组(同种异体移植有CTLA4Ig基因)和对照组(非CTLA4Ig基因转染)。在实验组中,供体小肠在移植前通过上肠系膜内动脉经脂质体载体包装的CTLA4Ig cDNA进行离体灌注,移植后小肠移植物中CTLA4Ig的表达通过免疫组织学评估。移植后第3、7和10天,收集每组同种异体移植物用于组织学检查和凋亡检测。结果:CTLA4Ig cDNA处理的小肠同种异体移植物在移植后表现出丰富的CTLA4Ig表达。在对照同种异体移植中,在移植后第7天出现了Ⅰ级急性排斥反应,在移植后第10天出现了Ⅱ级急性排斥反应,并且与进行性排斥反应平行的凋亡小肠上皮细胞的数量急剧增加。相反,用CTLA4Ig cDNA处理的同种异体移植物显示出非特异性的组织学变化,并且移植后仅发现了少数凋亡性肠上皮细胞。结论:小肠同种异体移植局部CTLA4Ig基因转染是可行的,同种异体移植中局部CTLA4Ig表达可防止移植后急性排斥反应。

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