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The establishment of chronic lung rejection model using rat left lung allotransplantation

大鼠同种异体左肺移植慢性肺排斥反应模型的建立

基本信息

批准号：
07671461
负责人：
TAKAO Motoshi
金额：
$ 0.32万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671461/
关键词：
Lung transplantation Chronic rejection Rat Ob bronchiolitis Cyclosporine A Interleukin 2 Tracheal allograft in Omentum 閉塞性細気管支炎

项目摘要

(PURPOSE) To promote the experiment work on obliterative bronchiolitis (OB) syndrome following lung transplantation (LTx), we planed to establish the chronic lung rejection model using rats. (EXPERIMENTS) Left lung grafts will be orthotopically transplanted in the thorax, WKAH-to-F344 as allotransplanted model. All rats receive CsA dissolved in olive oil intramuscularly in a dosage of 25mg/kg body weight until day 14 after LTx. Thereafter they did not any immunosuppression until week 16 after Ltx. They had any histological finding of OB in transplanted lung. This may be explained by the fact that rat had no acute lung rejection followed by the discontinuation of immunosuppression, because rats are easily induced to be imunological tolerant (permanent graft acceptance of the allogenic LTx) by short term immunosuppression after trasplantation. Therefore, we examined whether rIL-2 injection may induce acute rejection in transplanted rat under immunological tolerance due to cyclosporine A or not. To simplify the experimental model, we used heterotopical tracheal transplantation into omentum, using BN-to-LEW as allotransplanted model. Group I (no immunosuppression) had airway obstruction of tracheal allografts at 4 weeks after transplantation. Group II (received cyclosporine A 25mg/kg injection at days 2 and 3 after transplantation) had patency of tracheal lumen and normal airway epithelium. Group III (received rIL-2 injection in Group II) showed airway obstruction of tracheal allograft in IL-2 dose-dependent fashion until 40,000 IU/day for 10days. These results show that airway obstruction of tracheal allografts may be related to immunological reaction, and rIL-2 could reverse immunological tolerance due to cyclosporine A in rat allotransplantation. Therefore rIL-2 injection might induce acute rejection to lung-transplanted rat under immunological tolerance due to cyclosporine A injection after Ltx and cause OB on trasplanted lung.

（目的）为了进一步开展肺移植后闭塞性细支气管炎（OB）综合征的实验工作，我们拟建立大鼠慢性肺排斥反应模型。（实验）将左肺移植物在胸腔内原位移植，以whah -to- f344作为同种异体移植模型。所有大鼠均以25mg/kg体重的剂量肌肉注射溶解于橄榄油中的CsA，直至LTx后第14天。此后，直到Ltx后第16周才出现免疫抑制。移植肺均有OB的组织学发现。这可能是由于移植后短期免疫抑制容易诱导大鼠产生免疫耐受（对同种异体LTx的永久性移植物接受），因此大鼠在停止免疫抑制后没有出现急性肺排斥反应。因此，我们研究il -2注射是否会引起环孢素A免疫耐受大鼠的急性排斥反应。为了简化实验模型，我们采用异位气管大网膜移植，以bn - lew为异体移植模型。ⅰ组（无免疫抑制）同种异体气管移植术后4周出现气道阻塞。第二组（移植后第2、3天注射环孢素A 25mg/kg）气管管腔通畅，气管上皮正常。III组（II组接受IL-2注射）显示同种异体气管移植物出现IL-2剂量依赖性气道阻塞，直至40000 IU/天，持续10天。这些结果表明，同种异体气管移植的气道阻塞可能与免疫反应有关，而il -2可以逆转同种异体气管移植大鼠对环孢素A的免疫耐受。因此，il -2注射可引起肺移植大鼠肺移植术后环孢素A免疫耐受的急性排斥反应，引起移植肺OB。