上海交通大学学报（医学版）

›› 2010, Vol. 30 ›› Issue (7): 779-.

• 论著（基础研究） • 上一篇    下一篇

环孢素对心脏移植大鼠急性排斥反应及血清IDO活性的影响

郭 庆, 黄君龄, 王祥慧, 徐 达, 周佩军, 邵 琨   

  1. 上海交通大学 医学院瑞金医院肾脏移植中心, 上海 200025
  • 出版日期:2010-07-25 发布日期:2010-07-26
  • 通讯作者: 王祥慧, 电子信箱: wxh4270@sina.com。
  • 作者简介:郭 庆（1983—）, 男, 硕士生；电子信箱: guoqing777@126.com。
  • 基金资助:

    卫生部国际交流与合作课题（IHECC07-001）

Effects of ciclosporin on acute rejection and serum IDO activity of rats with heart transplantation

GUO Qing, HUANG Jun-ling, WANG Xiang-hui, XU Da, ZHOU Pei-jun, SHAO Kun   

  1. Renal Transplantation Center, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China
  • Online:2010-07-25 Published:2010-07-26
  • Supported by:

    Foundation of International Communication and Cooperation of the Ministry of Health of China, IHECC07-001

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摘要：

目的 探讨不同剂量的强效免疫抑制剂环孢素(CsA)对同种异基因心脏移植大鼠急性排斥反应程度和血清吲哚胺2，3双加氧酶（IDO）活性的影响。方法 分别以SD和Wistar大鼠为供、受体，建立同种异基因大鼠颈部异位心脏移植模型。18只受体大鼠随机分为对照组、低剂量CsA组 (CsA 2 mg·kg-1·d-1）和高剂量CsA组(CsA 15 mg·kg-1·d-1），每组6只。术后第7天，所有受体大鼠经腹主动脉采集血样后处死，取移植心脏制备组织学检查标本。ELISA法检测血清白介素2（IL-2）和γ干扰素（IFN-γ）水平；高压液相色谱法检测血清犬尿氨酸和色氨酸浓度，计算两者比值并以此估算IDO活性。移植心脏标本常规HE染色，采用Stanford 标准进行急性排斥反应程度分级。结果 三组血清IL-2和IFN-γ水平以及IDO活性比较显示，对照组>低剂量CsA组>高剂量CsA组，差异均有统计学意义（P＜0.05或P＜0.01）。三组移植心脏急性排斥反应程度分级结果显示，对照组>低剂量CsA组>高剂量CsA组，差异均有统计学意义（P＜0.01）。结论 CsA可明显减轻同种异基因大鼠移植心脏急性排斥反应程度并降低血清IDO活性，两者变化趋势一致且与CsA的使用剂量有关。提示血清IDO活性监测有可能成为一种无创性移植器官急性排斥反应及其程度的预测和评估方法。

关键词: 环孢素, 急性排斥反应, 吲哚胺2, 3双加氧酶, 心脏移植, 大鼠

Abstract:

Objective To investigate the effects of different doses of immunodepressant cyclosporine (CsA) on the degree of acute rejection and activity of serum indoleamine 2, 3-dioxygenase (IDO) in rats with allogene heart transplantation. Methods With SD and Wistar rats as donors and recipients, respectively, rat cervical heterotopic heart transplantation models were established. Eighteen recipients were randomly divided into control group (n=6), low-dose CsA group (CsA 2 mg·kg-1·d-1, n=6) and high-dose CsA group (CsA 15 mg·kg-1·d-1, n=6). Blood samples were taken from abdominal aorta of recipients on the seventh day after transplantation, and heart transplants were harvested for histological examinations. Serum interleukin-2 (IL-2) and interferon-γ (IFN-γ) levels were detected by ELISA, serum kynurenine and tryptophan concentrations were measured by high-pressure liquid chromatography, and the ratios of kynurenine to tryptophan were calculated to estimate the IDO activity. Routine HE staining was performed on samples of heart transplants, and degree of acute rejection was determined with Stanford criteria. Results For serum IL-2 and IFN-γ levels and IDO activity, there were significant differences among groups (P＜0.05 or P＜0.01）, with control group>low-dose CsA group>high-dose CsA group. For degree of acute rejection of heart transplantation, there were significant differences among groups (P＜0.01）, with control group>low-dose CsA group>high-dose CsA group (P＜0.01）. Conclusion CsA may decrease the degree of acute rejection and serum IDO activity in rats with allogene heart transplantation in a dose-dependent manner, and the change of degree of acute rejection is consistent with that of IDO activity. Serum IDO activity may serve as a non-invasive indicator for the prediction and evaluation of acute rejection of transplantation.

Key words: cyclosporine, acute rejection, indoleamine 2, 3-dioxygenase, heart transplantation, rat