Thalidomide treatment prevents chronic graft rejection after aortic transplantation in rats - an experimental study.

Thalidomide treatment prevents chronic graft rejection after aortic transplantation in rats - an experimental study.
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DOI:
10.1111/tri.13004
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发表时间:
2017-11
期刊:
Transplant international : official journal of the European Society for Organ Transplantation
影响因子:
--
通讯作者:
Bernstein D
Bernstein D
中科院分区:
其他
文献类型:
--
作者:
Miller KK;Wang D;Hu X;Hua X;Deuse T;Neofytou E;Renne T;Velden J;Reichenspurner H;Schrepfer S;Bernstein D

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心脏同种异体移植血管病 (CAV) 影响约 30% 的心脏移植患者在移植后 5 年的情况。迄今为止,CAV 的治疗或预防方案很少,而且都不是非常有效。该研究的目的是调查沙利度胺对 CAV 发展的影响。在同种异体 F344 或同系 Lew 大鼠(n=6/组)的原位主动脉移植中评估沙利度胺治疗对慢性排斥反应的影响。移植后 30 天,动物不接受治疗或接受沙利度胺治疗,并通过组织学(三色和免疫组织化学)和移植物内细胞因子测量来确定移植物 CAV 的证据。移植后接受沙利度胺治疗的动物表现出管腔闭塞显着减少,同时移植物主动脉中层的平滑肌细胞(SMC)得到拯救。沙利度胺通过防止血管 SMC 去分化来抵消新生内膜增生。沙利度胺治疗后移植物内细胞因子水平的测量显示,基质金属蛋白酶 8 (MMP-8) 和单核细胞趋化蛋白 1 (MCP-1) 下调,细胞因子分别参与组织重塑和炎症。重要的是,没有观察到沙利度胺的负面副作用。沙利度胺治疗可防止啮齿动物模型中 CAV 的发展,因此在临床应用中可能有助于预防移植后心脏排斥反应。
Cardiac allograft vasculopathy (CAV) affects approximately 30% of cardiac transplant patients at five years post-transplantation. To date there are few CAV treatment or prevention options, none of which are highly effective. The aim of the study was to investigate the effect of thalidomide on the development of CAV. The effect of thalidomide treatment on chronic rejection was assessed in rat orthotopic aortic transplants in allogeneic F344 or syngeneic Lew rats (n=6/group). Animals were left untreated or received thalidomide for 30 days post-transplant, and evidence of graft CAV was determined by histology (trichrome and immunohistochemistry) and intragraft cytokine measurements. Animals that received thalidomide treatment post-transplant showed markedly reduced luminal obliteration, with concomitant rescue of smooth muscle cells (SMCs) in the aortic media of grafts. Thalidomide counteracted neointimal hyperplasia by preventing dedifferentiation of vascular SMCs. Measurement of intragraft cytokine levels after thalidomide treatment revealed down-regulation of matrix metalloproteinase 8 (MMP-8) and monocyte chemotactic protein 1 (MCP-1), cytokines involved in tissue remodeling and inflammation, respectively. Importantly, no negative side effects of thalidomide were observed. Thalidomide treatment prevents CAV development in a rodent model and is therefore potentially useful in clinical applications to prevent post-transplant heart rejection.
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