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多克隆抗胸腺细胞球蛋白对非人类灵长类动物模型缺血再灌注损伤的影响。

Influence of polyclonal anti-thymocyte globulins upon ischemia-reperfusion injury in a non-human primate model.

作者信息

Beiras-Fernandez Andres, Chappell Daniel, Hammer Claus, Thein Eckart

机构信息

Institute for Surgical Research, Ludwig-Maximilians-University, Munich, Germany.

出版信息

Transpl Immunol. 2006 Apr;15(4):273-9. doi: 10.1016/j.trim.2006.02.003. Epub 2006 Mar 24.

DOI:10.1016/j.trim.2006.02.003
PMID:16635749
Abstract

BACKGROUND

Polyclonal anti-thymocyte globulins (ATGs) are used to induce immunosuppression and to treat acute rejection after transplantation. ATGs induce apoptosis and in peripheral T-lymphocytes having the potential to inhibit leukocyte adhesion. We analysed the influence of three different ATGs upon the microvasculature and the different cell-subpopulations after ischemia/reperfusion (IRI).

MATERIALS AND METHODS

Extremities of cynomolgus monkeys were surgically isolated and flushed with Ringer's lactate at 4 degrees C. After 60 min of ischemia the limbs were reperfused with matching human blood. ATGs were added to the blood 30 min prior to the reperfusion. Four groups were generated: Tecelac-ATG group, Fresenius(S)-ATG group, Thymoglobulin-ATG group and a control group. Blood analyses were performed in blood samples taken after the beginning of the reperfusion. Biopsies from muscular tissue were obtained after the experiments.

RESULTS

The number of circulating leukocytes was lower in the ATG-groups than in control. Morpho-cytological analyses showed depletion of peripheral lymphocytes. Histological examination showed less tissue damage, reduced presence of fibrin and adherent thrombocytes in the ATG-treated groups. Leukocyte infiltration, both in muscle and vascular structures, was significantly diminished in the ATG-groups in comparison to control.

DISCUSSION

Our results show that ATGs have a favourable impact on early mechanisms of IRI. ATGs showed a reduction of the number of adherent leukocytes and muscle infiltrates suggesting that preoperative therapy with ATGs may have an advantageous effect on primary non-function and on chronic rejection as well as a positive influence upon IRI.

摘要

背景

多克隆抗胸腺细胞球蛋白(ATG)用于诱导免疫抑制并治疗移植后的急性排斥反应。ATG可诱导凋亡,并在外周血T淋巴细胞中具有抑制白细胞黏附的潜力。我们分析了三种不同的ATG对缺血/再灌注(IRI)后微血管和不同细胞亚群的影响。

材料与方法

对食蟹猴的肢体进行手术分离,并用4℃的乳酸林格液冲洗。缺血60分钟后,用匹配的人血对肢体进行再灌注。在再灌注前30分钟将ATG加入血液中。分为四组:Tecelac-ATG组、费森尤斯(S)-ATG组、胸腺球蛋白-ATG组和对照组。在再灌注开始后采集的血样中进行血液分析。实验结束后从肌肉组织中获取活检标本。

结果

ATG组循环白细胞数量低于对照组。形态细胞学分析显示外周淋巴细胞减少。组织学检查显示,ATG治疗组的组织损伤较轻,纤维蛋白和黏附血小板的存在减少。与对照组相比,ATG组肌肉和血管结构中的白细胞浸润均显著减少。

讨论

我们的结果表明,ATG对IRI的早期机制有有利影响。ATG显示黏附白细胞数量和肌肉浸润减少,这表明术前使用ATG治疗可能对原发性无功能和慢性排斥反应有有利影响,以及对IRI有积极影响。

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