Riboflavin-mediated reduction of oxidant injury, rejection, and vasculopathy after cardiac allotransplantation
Riboflavin-mediated reduction of oxidant injury, rejection, and vasculopathy after cardiac allotransplantation
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DOI：
10.1097/01.tp.0000256283.06469.d4
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发表时间：
2007-03-27
期刊：
影响因子：
6.2
通讯作者：
Pinsky, David J.
中科院分区：
文献类型：
--
作者：
Iwanaga, Koichiro;Hasegawa, Tomomi;Pinsky, David J.
背景。核黄素是一种众所周知的营养补充剂，已被证明具有抗氧化特性并保护组织免受氧化损伤。我们假设，在心脏缺血再灌注 (I/R) 期间给予核黄素可能会减少同种异体移植后随后的急性排斥反应和冠状动脉同种异体移植血管病变 (CAV)。方法。使用小鼠异位心脏移植模型来测试核黄素是否改善 I/R 损伤和急/慢性排斥反应。结果。核黄素显着减少 I/R 损伤引起的氧化剂产生和炎症介质产生，丙二醛、髓过氧化物酶活性和肿瘤坏死因子 α 水平降低就证明了这一点。在同种异体移植后的早期，核黄素的施用还可以提高移植物的存活率并抑制T细胞浸润和供体反应性同种抗体的形成。采用免疫抑制（术前抗鼠 CD4 和抗 CD8）的小鼠长期同种异体心脏移植模型来研究核黄素在 60 天时对 CAV 的作用。与盐水处理的移植物相比，核黄素处理的移植物表现出冠状动脉管腔闭塞严重程度显着降低（17.4 +/- 1.8% vs. 43.5 +/- 5.6%，P=0.0012）。然而，在这种慢性模型中，核黄素对减少供体反应性同种抗体没有显着作用。结论。这些数据表明，核黄素可改善早期 I/R 损伤并减少 CAV 的发展，这很可能是由于同种异体抗原无关的作用，例如减少了早期移植物氧化应激。在心脏同种异体移植中施用核黄素似乎是减少早期移植物脂质过氧化、白细胞浸润和细胞因子产生以及抑制心脏同种异体移植血管病变的晚期发展的有效手段。
Background. Riboflavin is a well-known nutritional supplement that has been shown to exhibit antioxidant properties and protect tissue from oxidative damage. We hypothesized that riboflavin given during cardiac ischemia-reperfusion (I/R) might reduce subsequent acute rejection, after allotransplantation, and coronary allograft vasculopathy (CAV).Methods. A murine heterotopic cardiac transplantation model was used to test whether riboflavin improves I/R injury and acute/chronic rejection.Results. Riboflavin significantly reduced oxidant production and inflammatory mediator production induced by I/R injury, as evidenced by decreased levels of malondialdehyde, myeloperoxidase activity, and tumor necrosis factor alpha. Administration of riboflavin also improved graft survival and suppressed T-cell infiltration and donor-reactive alloantibody formation during the early period after allotransplantation. A murine long-term cardiac allograft model using immunosuppression (preoperative anti-murine CD4 and anti-CD8) was employed to investigate the effect of riboflavin against CAV at 60 days. Riboflavin-treated grafts exhibited a significant decrease in the severity of coronary artery luminal occlusion as compared with saline-treated grafts (17.4 +/- 1.8% vs. 43.5 +/- 5.6%, P=0.0012). However, there was no significant effect of riboflavin to reduce donor-reactive alloantibodies in this chronic model.Conclusions. These data indicate that riboflavin improves early I/R injury and reduces the development of CAV, most likely due to alloantigen-independent effects such as reduced early graft oxidant stress. Riboflavin administered in the setting of cardiac allograft transplantation appears to be a powerful means to reduce early graft lipid peroxidation, leukocytic infiltration, and cytokine production as well as to suppress the late development of cardiac allograft vasculopathy.