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

Analysis of simultaneous allotransplantation of small intestine and liver

同种异体小肠和肝脏同步移植分析

基本信息

批准号：
03670586
负责人：
FUKUZAWA Masahiro
金额：
$ 1.34万
依托单位：
Osaka 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：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670586/
关键词：
Small intestine allotransplantation FK506 T cell function

项目摘要

The first series of experiments examined the effect of intra-muscular(im) administration of FK506 on small intesitine allo-graft survival. DA and LEW rats were used as small intestine donors and recipients. FK506 (0.3mg/kg, 1.0mg/kg or 2mg/kg) was given im for 14 days after transplantation. The results clearly demonstrated that the rejection of small intestine allograft was suppressed by FK506 at the dosage of 2.0mg/kg per day, whereas, as a complication of this drugs, all rats died of pneumonia. In order to diminish the requirements for high doses of FK506 in recipients of small intestine allograft, we tried to investigate the effect simultaneous allotransplantation of small intestine and liver. However, recipients died of infection. We changed the protocol to analyze the effect of donor-specific transfusion (DST) and FK506 on small intestine allotransplantation. Recipients (LEW) received 1.5 ml of freshly drawn DA blood iv on day -8 with respect to grafting ( day 0 ). FK506 was administered at a dose of 1.0mg/kg per day from day -8 to day -4, and at 0.3mg/kg per day from day 0 to day +14. The results clearly demonstrated that FK506 combined with DST is effective to prevent acute rejection. Longterm allograft survival could be obtained by conditioning with combined DST and low-dose FK506. To test for in vivo effects of DST+FK506 on T cell function , CTL and IL-2 production were tested in rats treated with DST+FK506. The results suggested that DST+FK506 resulted in selective inhibition of anti-DA T-cell responses without suppressing T-cell responses to third party alloantigens.

第一系列实验检查了肌内 (im) 施用 FK506 对小肠同种异体移植物存活的影响。 DA 和 LEW 大鼠被用作小肠供体和受体。移植后肌内给予FK506（0.3mg/kg、1.0mg/kg或2mg/kg）14天。结果清楚地表明，每天2.0mg/kg剂量的FK506可抑制小肠同种异体移植物的排斥反应，而作为该药物的并发症，所有大鼠均死于肺炎。为了减少小肠同种异体移植受者对高剂量FK506的需求，我们尝试研究小肠和肝脏同时同种异体移植的效果。然而，接受者死于感染。我们改变了方案来分析供体特异性输血 (DST) 和 FK506 对小肠同种异体移植的影响。接受者(LEW)在移植第-8天(第0天)接受1.5ml新鲜抽取的DA血液静脉注射。 FK506从第-8天到第-4天以每天1.0mg/kg的剂量施用，并且从第0天到第+14天以每天0.3mg/kg的剂量施用。结果清楚地表明FK506联合DST可有效预防急性排斥反应。通过联合 DST 和低剂量 FK506 进行调理可以获得长期同种异体移植物存活。为了测试 DST+FK506 对 T 细胞功能的体内影响，在用 DST+FK506 治疗的大鼠中测试了 CTL 和 IL-2 的产生。结果表明，DST+FK506 导致选择性抑制抗 DA T 细胞反应，而不抑制 T 细胞对第三方同种抗原的反应。