吲哚胺2,3-双加氧酶作为大鼠原位肝移植后急性排斥反应的预测指标

Indoleamine 2,3-dioxygenase as a predictor of acute rejection after orthotopic liver transplantation in rat model.

作者信息

Weng M-Z, Xu Y-G, Zhang Y, Zhang J-Y, Quan Z-W, Xu J-M, Peng Z H

机构信息

Department of General Surgery of Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Transplant Proc. 2011 Dec;43(10):3969-72. doi: 10.1016/j.transproceed.2011.09.061.

DOI:10.1016/j.transproceed.2011.09.061

PMID:22172881

Abstract

BACKGROUND

Indoleamine 2,3-dioxygenase (IDO) had been reported to correlate with immunomodulatory effects and the severity of acute rejection (AR) after liver transplantation. We sought to study the time course of IDO mRNA expression in peripheral blood to diagnose AR.

METHODS

The rats were divided into 4 groups each consisting of 32 rats: group A, isograft Sprague-Dawley (SD)-SD); group B, acute rejection model (SD-Wistar); group C, cyclosporine (CsA)-induced acceptance model (SD-Wistar rats treated with CsA, and group D, short-term CsA-treated model. The peripheral blood and liver tissue samples were obtained on the day of operation as well as 1, 2, 3, 4, 5, 7, and 9 days thereafter. We performed reverse-transcription polymerase chain reaction, pathologic studies, and serum tests.

RESULTS

Groups A and C showed low levels of IDO mRNA as well as normal values of aspartate transaminase (AST), total bilirubin (T-BIL), and alkaline phosphatase (ALP) without AR. Group B showed a dramatic rise in IDO mRNA on day 2 with increased AST, T-BIL, and ALP at day 4 and mild AR on day 5. Group D, showed dramatically up-regulated IDO mRNA on day 4 with significantly increased AST, T-BIL, and ALP day 5 and mild AR detected on day 7. The expression of IDO gene in peripheral blood tightly correlated with the severity of acute rejection (P<.001).

CONCLUSIONS

Compared with the pathologic study detection of IDO mRNA in peripheral blood diagnosed AR in the rat model at an earlier stage.

摘要

背景

据报道，吲哚胺2,3-双加氧酶（IDO）与肝移植后的免疫调节作用及急性排斥反应（AR）的严重程度相关。我们试图研究外周血中IDO mRNA表达的时间进程以诊断AR。

方法

将大鼠分为4组，每组32只：A组，同基因移植（Sprague-Dawley（SD）大鼠之间）；B组，急性排斥模型（SD大鼠与Wistar大鼠之间）；C组，环孢素（CsA）诱导的耐受模型（用CsA处理的SD-Wistar大鼠）；D组，短期CsA处理模型。在手术当天以及术后1、2、3、4、5、7和9天采集外周血和肝组织样本。我们进行了逆转录聚合酶链反应、病理研究和血清检测。

结果

A组和C组IDO mRNA水平较低，天冬氨酸转氨酶（AST）、总胆红素（T-BIL）和碱性磷酸酶（ALP）值正常，无AR发生。B组在第2天IDO mRNA急剧升高，第4天AST、T-BIL和ALP升高，第5天出现轻度AR。D组在第4天IDO mRNA显著上调，第5天AST、T-BIL和ALP显著升高，第7天检测到轻度AR。外周血中IDO基因的表达与急性排斥反应的严重程度密切相关（P<0.001）。