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

[目的]探讨小肠移植后胆汁酸成分变化对评价大鼠小肠功能的意义。[方法](1)将体重250~300g的雄性Lewis大鼠与Lewis大鼠的全小肠同位异位移植，以Brown-挪威大鼠的小肠为排斥模型。移植物的动脉与受体的腹主动脉吻合，门静脉与受体的门静脉(P-P)或下腔静脉(P-V)吻合。同种异体移植模型采用P-V吻合术。肠以吻合为主。(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胆汁中24种胆汁酸的含量.(3)建立排斥模型动物模型后，随机分为4组，每组8只，分别为假手术组、异体移植组(Lew-Lew)、异体移植组(13N-Lew)、FK506组(0.5 mg/kg i.m)。[结果](L)在同种异体移植模型中，P-V组胆汁排出量无明显变化，胆汁和血清胆汁酸浓度升高，且P-V组高于P-P组。甘氨酸结合物术后2周升高，术后4周恢复正常。二次胆汁酸在术后2~4周有升高趋势。(2)在同种异体移植(排斥)模型中，术后1周，当移植肠壁组织学显示中度急性排斥反应时，第3组次级胆汁酸(脱氧胆酸)升高，初级胆汁酸(胆酸)降低，而应用FK506的第4组未见上述变化。

[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.