Division of Nephrology, São José do Rio Preto Medical School, Av. Brigadeiro Faria Lima 5416, São José do Rio Preto, São Paulo, 15090-000, Brazil.
J Mol Med (Berl). 2011 Jan;89(1):51-63. doi: 10.1007/s00109-010-0684-4. Epub 2010 Oct 16.
Inflammation is currently recognized as a key mechanism in the pathogenesis of renal ischemia-reperfusion (I/R) injury. The importance of infiltrating neutrophil, lymphocytes, and macrophage in this kind of injury has been assessed with conflicting results. Annexin 1 is a protein with potent neutrophil anti-migratory activity. In order to evaluate the effects of annexin A1 on renal I/R injury, uninephrectomized rats received annexin A1 mimetic peptide Ac2-26 (100 μg) or vehicle before 30 min of renal artery clamping and were compared to sham surgery animals. Annexin A1 mimetic peptide granted a remarkable protection against I/R injury, preventing glomerular filtration rate and urinary osmolality decreases and acute tubular necrosis development. Annexin A1 infusion aborted neutrophil extravasation and attenuated macrophage infiltration but did not prevent tissue lymphocyte traffic. I/R increased annexin A1 expression (assessed by transmission electron microscopy) in renal epithelial cells, which was attenuated by exogenous annexin A1 infusion. Additionally, annexin A1 reduced I/R injury in isolated proximal tubules suspension. Annexin A1 protein afforded striking functional and structural protection against renal I/R. These results point to an important role of annexin A1 in the epithelial cells defense against I/R injury and indicate that neutrophils are key mediators for the development of tissue injury after renal I/R. If these results were confirmed in clinical studies, annexin A1 might emerge as an important tool to protect against I/R injury in renal transplantation and in vascular surgery.
炎症目前被认为是肾缺血再灌注（I/R）损伤发病机制中的一个关键机制。浸润中性粒细胞、淋巴细胞和巨噬细胞在这种损伤中的重要性已经得到了评估，但结果存在矛盾。膜联蛋白 1 是一种具有强大中性粒细胞抗迁移活性的蛋白质。为了评估膜联蛋白 A1 对肾 I/R 损伤的影响，单侧肾切除术大鼠在肾动脉夹闭前 30 分钟接受膜联蛋白 A1 模拟肽 Ac2-26（100μg）或载体，并与假手术动物进行比较。膜联蛋白 A1 模拟肽对 I/R 损伤具有显著的保护作用，可防止肾小球滤过率和尿渗透压降低以及急性肾小管坏死的发生。膜联蛋白 A1 输注可阻止中性粒细胞渗出，并减轻巨噬细胞浸润，但不能防止组织淋巴细胞迁移。I/R 增加了肾上皮细胞中膜联蛋白 A1 的表达（通过透射电子显微镜评估），而外源性膜联蛋白 A1 输注可减弱这种表达。此外，膜联蛋白 A1 降低了分离的近端肾小管悬浮液中的 I/R 损伤。膜联蛋白 A1 蛋白对肾 I/R 具有显著的功能和结构保护作用。这些结果表明膜联蛋白 A1 在肾上皮细胞防御 I/R 损伤中起重要作用，并表明中性粒细胞是肾 I/R 后组织损伤发展的关键介质。如果这些结果在临床研究中得到证实，那么膜联蛋白 A1 可能成为保护肾移植和血管手术中 I/R 损伤的重要工具。
