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Significance of glutathione and bile acids metabolism for assessment of graft function after small intestinal transplantation in rats.

谷胱甘肽和胆汁酸代谢对评估大鼠小肠移植后移植物功能的意义。

基本信息

批准号：
09671315
负责人：
KOBAYASHI Nobuaki
金额：
$ 2.18万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

[Aim] The aim of this research project is to study the significance of changes of bile acid component for assessment of grail function after small intestinal transplantation.[Method] (1) Male Lewis rats, weighing 250-300g, were iso-transplanted orthotropically with entire small intestine of Lewis rats, and were aim-transplanted with small intestine of Brown-Norway rats as rejection model. Artery of the graft was anastomosed to abdominal aorta of the recipient, and portal vein of the graft was anastomosed to the portal vein of recipient(P-P), or to the inferior vena cava(P-V) in iso-graft model. In allo-graft model, P-V anastomosis was performed. Intestine was primarily anastomosed. (2) One, two and four weeks after operation, bile and blood samples were collected, and 24 kinds of bile acids were measured by HPLC.(3) The animals with rejection models were devided into 4 groups (each n=8), as follows ; Group 1 : sham operation, Group 2 : iso-graft(Lew-Lew), Group 3 : allo-graft(13N-Lew), Group 4 : FK506(O.5mg/Kg i.m.) was administrated to Group 3 every day following operation.[Results] (l)ln iso-grafted model, bile out put did not change, bile acid concentration in bile and serum increased and showed higher level in P-V group than in P-P group. Glycine conjugates increased 2 weeks after, and normalized 4 weeks after operation. Secondary bile acids tended to increase during 2 to 4 weeks after operation. (2) ln allo-grafted(rejection) model, at the time of 1 week after operation when graft gut wall revealed moderate acute rejection histopathologically, secondary bile acid(deoxycholic acid) increased and primary bile acid(cholic acid) decreased in Group 3, and these changes were not seen in Group 4, in which FK506 was administered.[Conclusion] The changes of increased secondary bile acid and decreased primary bile acid in serum and bile after small intestinal transplantation may inform the occurrence of rejection.

[Aim]本研究旨在探讨小肠移植术后胆汁酸成分的变化对评价移植肠功能的意义。[方法]（1）雄性刘易斯大鼠，体质量250- 300 g，同向移植刘易斯大鼠全小肠，定向移植Brown-Norway大鼠小肠作为排斥模型。移植物动脉与受体腹主动脉吻合，移植物门静脉与受体门静脉吻合（P-P），同种移植物与下腔静脉吻合（P-V）。在同种异体移植模型中，进行P-V吻合。主要是肠道坏死。(2)分别于术后1、2、4周采集胆汁和血样，用高效液相色谱法测定24种胆汁酸。(3)排斥模型动物分为4组（每组8只）：假手术组（1组）、同种异体移植组（13 N-Lew组）、假手术组（2组）、FK 506组（0.5mg/Kg i.m.）第3组术后每天给药一次。[结果]（1）在同种移植模型中，P-V组胆汁排出量无明显变化，胆汁和血清中胆汁酸浓度升高，且P-V组高于P-P组。术后2周，甘氨酸结合物增加，术后4周恢复正常。继发胆汁酸在术后2 ~ 4周呈上升趋势。(2)在同种异体移植（排斥）模型中，术后1周移植肠壁组织病理学显示中度急性排斥时，第3组的继发性胆汁酸（脱氧胆酸）增加，原发性胆汁酸（胆酸）减少，而给予FK 506的第4组未观察到这些变化。[结论]小肠移植术后血清和胆汁中继发性胆汁酸升高和原发性胆汁酸降低的变化可能与排斥反应的发生有关。