Weber T, Kalbhenn T, Herrmann G, Hanisch E
Department of General and Abdominal Surgery, University Hospital, Frankfurt a.M., Germany.
Transplantation. 1997 Sep 15;64(5):705-8. doi: 10.1097/00007890-199709150-00007.
In this study we have analyzed the local immunosuppression with budesonide, a topically selective glucocorticosteroid, in rats after orthotopic liver transplantation. Because of its high first-pass hepatic clearance budesonide can be given orally, achieving high intrahepatic and low systemic concentrations.
Using an acute rejection model from Dark Agouti (DA) to Lewis rats, the histomorphological degree of rejection was assessed on histological sections at the ninth postoperative day.
Livers of the DA to Lewis study group without immunosuppression revealed severe allograft rejection with vast cellular infiltrates, massive endothelialitis, and hepatocyte necrosis. In the three budesonide study groups (250 microg, 500 microg, and 1 mg/kg/day) a moderate to mild liver allograft rejection was seen. Rejection was most prominent in the 250 microg group, whereas the 1 g group showed almost no signs of rejection, similar to the Lewis to Lewis control group. Aspartate and alanine transaminase (sGOT, sGPT) as well as alkaline phosphatase serum levels correlated with the degree of rejection, achieving highest levels in the DA to Lewis group without immunosuppression. Animals treated with 1 g of budesonide had serum levels similar to Lewis to Lewis control animals.
These results implicate a beneficial effect of local immunosuppression with budesonide in rats based on the histomorphological degree of liver allograft rejection.
在本研究中，我们分析了局部选择性糖皮质激素布地奈德对大鼠原位肝移植后的局部免疫抑制作用。由于布地奈德具有较高的首过肝清除率，因此可以口服给药，从而在肝内达到高浓度而在全身达到低浓度。
采用从黑褐大鼠（DA）到Lewis大鼠的急性排斥模型，在术后第9天对组织切片评估排斥反应的组织形态学程度。
未进行免疫抑制的DA到Lewis研究组的肝脏显示出严重的同种异体移植排斥反应，伴有大量细胞浸润、广泛的内皮炎和肝细胞坏死。在三个布地奈德研究组（250微克、500微克和1毫克/千克/天）中，观察到中度至轻度的肝同种异体移植排斥反应。排斥反应在剂量为250微克的组中最为明显，而剂量为1毫克的组几乎没有排斥反应迹象，类似于Lewis到Lewis对照组。天冬氨酸转氨酶和丙氨酸转氨酶（sGOT、sGPT）以及碱性磷酸酶血清水平与排斥反应程度相关，在未进行免疫抑制的DA到Lewis组中达到最高水平。接受1毫克布地奈德治疗的动物血清水平与Lewis到Lewis对照动物相似。
基于肝同种异体移植排斥反应的组织形态学程度，这些结果表明布地奈德对大鼠进行局部免疫抑制具有有益作用。
