Department of Nephrology and Hypertension, Medical School Hannover, Germany.
J Am Soc Nephrol. 2011 Oct;22(10):1887-96. doi: 10.1681/ASN.2011010031. Epub 2011 Aug 12.
Renal ischemia-reperfusion contributes to reduced renal allograft survival. The peptide Bβ(15-42), a breakdown product of fibrin, attenuates inflammation induced by ischemia-reperfusion in the heart by competitively blocking the binding of leukocytes to endothelial VE-cadherin, but whether it could improve outcomes in renal transplantation is unknown. Here, we tested the ability of Bβ(15-42) to ameliorate the effects of renal ischemic injury during allogenic kidney transplantation in mice. In our renal transplantation model (C57BL/6 into BALB/c mice), treatment with Bβ(15-42) at the time of allograft reperfusion resulted in significantly improved survival of recipients during the 28-day follow-up (60% versus 10%). Bβ(15-42) treatment decreased leukocyte infiltration, expression of endothelial adhesion molecules, and proinflammatory cytokines. Treatment significantly attenuated allogenic T cell activation and reduced cellular rejection. Moreover, Bβ(15-42) significantly reduced tubular epithelial damage and apoptosis, which we reproduced in vitro. These data suggest that Bβ(15-42) may have therapeutic potential in transplant surgery by protecting grafts from ischemia-reperfusion injury.
肾缺血再灌注导致移植肾存活率降低。纤维蛋白的降解产物肽 Bβ(15-42) 通过竞争性结合白细胞与内皮 VE-钙黏蛋白，从而减轻缺血再灌注引起的心肌炎症，但它是否能改善肾移植的结果尚不清楚。在这里，我们测试了 Bβ(15-42) 在小鼠同种异体肾移植中减轻肾缺血损伤的能力。在我们的肾移植模型（C57BL/6 到 BALB/c 小鼠）中，在同种异体移植物再灌注时给予 Bβ(15-42)治疗，可显著提高 28 天随访期间受者的存活率（60%对 10%）。Bβ(15-42)治疗可减少白细胞浸润、内皮黏附分子的表达和促炎细胞因子。治疗可显著抑制同种异体 T 细胞激活并减少细胞排斥。此外，Bβ(15-42)可显著减轻体外复制的肾小管上皮损伤和细胞凋亡。这些数据表明，Bβ(15-42)通过保护移植物免受缺血再灌注损伤，可能具有移植手术的治疗潜力。
