权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Synergistic effect of FK506 and calcium antagonist on small intestinal transplantation

FK506与钙拮抗剂对小肠移植的协同作用

基本信息

批准号：
02670581
负责人：
TAGUCHI Tomoaki
金额：
$ 1.41万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670581/
关键词：
small intestine allogeneic transplantation rejection FK506 calcium antagonist orthotopic heterotopic histology 小腸移植同種移植 KF506

项目摘要

One of the major obstacles for small intestinal transplabtation is the immunosuppression. FK506 is one of the most powerful immunosuppressive agents which has been shown to be more effective than ciclosporine in liver transplantation. Pittsburg group has tried about 60 cases of small bowel transplantation clinically using FK506. However, the graft survival for 2 years was less than 50%. Because FK506 is a calcium dependent immunosuppres-sive agent, synergistic effect with calcium antagonist is expected. Therefore, combination FK506 and Trifluoperazine (TFP : calmodulin inhibitor) was examined using rat model.Fully allogeneic rat transplanation was done using combination of WKAM (RT1^u) as a donor and Lewis(RT1^1) as a recipient. For graft survival, administration of FK506 0.5mg/kg/day or more was necessary. FK506 0.3mg/kg did not inhibit graft rejection. On the other hand, combination FK506 0.3mg/kg and TFP 3mg/kg were able to avoid graft rejection. The histological findings of the graft treated by FK506 0.3mg and TFP 3mg at 10 days after operation was almost same as those of the graft treated by FK506 0.5mg. The graft treated by FK506 0.3mg was shown to be rejected histologically. Recipients could not tolerate the administration of TFP more than 3mg/kg/day, because of appetite loss or respiratory insufficiency.In summary, synergistic effect of FK506 and TFP was revealed in this experiment. This combination will be hopeful for successful clinical small bowel transplantation.

小肠移植的主要障碍之一是免疫抑制。 FK506是最强大的免疫抑制剂之一，已被证明在肝移植中比环孢素更有效。匹兹堡小组已使用FK506临床尝试了约60例小肠移植。然而，移植物2年存活率不足50%。由于FK506是钙依赖性免疫抑制剂，因此预计与钙拮抗剂具有协同作用。因此，使用大鼠模型检查了FK506和三氟拉嗪（TFP：钙调蛋白抑制剂）的组合。使用WKAM（RT1^u）作为供体和Lewis（RT1^1）作为受体的组合进行完全同种异体大鼠移植。为了使移植物存活，需要施用0.5mg/kg/天或更多的FK506。 FK506 0.3mg/kg不抑制移植物排斥反应。另一方面，FK506 0.3mg/kg 和 TFP 3mg/kg 的组合能够避免移植物排斥。术后10天，FK506 0.3mg和TFP 3mg处理的移植物的组织学表现与FK506 0.5mg处理的移植物几乎相同。经过FK506 0.3mg处理的移植物在组织学上显示被排斥。由于食欲减退或呼吸功能不全，受者不能耐受超过3mg/kg/天的TFP给药。总之，本实验揭示了FK506和TFP的协同作用。这种组合将有望实现临床小肠移植的成功。