药物性纤溶酶原激活物抑制剂-1 抑制对鼠同种异体心脏移植物急性和慢性排斥反应的影响。
The effects of pharmacologic plasminogen activator inhibitor-1 inhibition in acute and chronic rejection in murine cardiac allografts.
机构信息
Department of Advanced Clinical Science and Therapeutics, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
出版信息
Transplantation. 2011 Jan 15;91(1):21-6. doi: 10.1097/tp.0b013e3181fd3c0f.
BACKGROUND
Acute rejection and graft arterial disease (GAD) in cardiac transplantation limit the long-term survival of recipients; these processes are enhanced by inflammation and thrombus formation. Plasminogen activator inhibitor (PAI)-1 is critical in the inflammation and thrombus formation. However, little is known about the effect of PAI-1 in heart transplantation. Thus, the objective was to clarify the role of PAI-1 in the progression of cardiac rejection.
METHODS
Murine hearts were heterotopically transplanted using major mismatch combinations for evaluation of acute rejection and class II mismatch combinations for the GAD. We administered the specific PAI-1 inhibitor (IMD-1622) into murine recipients after cardiac allografts.
RESULTS
Nontreated allografts of the major mismatch group were acutely rejected, whereas the PAI-1 inhibitor prolonged their survival. Although severe cell infiltration and intimal thickening with enhancement of inflammatory factors were observed in untreated allografts of class II mismatch group on day 60, the PAI-1 inhibitor attenuated these changes.
CONCLUSION
The PAI-1 inhibitor is potent for the suppression of both acute rejection and GAD.
背景
心脏移植后急性排斥反应和移植物动脉病（GAD）限制了受者的长期生存；炎症和血栓形成增强了这些过程。纤溶酶原激活物抑制剂（PAI-1）在炎症和血栓形成中起着关键作用。然而，关于 PAI-1 在心脏移植中的作用知之甚少。因此，本研究旨在阐明 PAI-1 在心脏排斥反应进展中的作用。
方法
使用主要不匹配组合进行异基因心脏移植，以评估急性排斥反应，并用 II 类不匹配组合评估 GAD。在心脏同种异体移植后，我们将特异性 PAI-1 抑制剂（IMD-1622）给予小鼠受者。
结果
未经治疗的主要不匹配组同种异体移植物发生急性排斥反应，而 PAI-1 抑制剂延长了其存活时间。尽管在第 60 天，未经治疗的 II 类不匹配组同种异体移植物中观察到严重的细胞浸润和内膜增厚，并增强了炎症因子，但 PAI-1 抑制剂减轻了这些变化。
结论
PAI-1 抑制剂可有效抑制急性排斥反应和 GAD。
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