Post-Graduation Program in Morphology, Federal University of São Paulo, São Paulo, SP, Brazil.
Inflamm Res. 2012 Mar;61(3):189-96. doi: 10.1007/s00011-011-0400-z. Epub 2011 Nov 19.
Cyclosporine (CsA) remains an important immunosuppressant for transplantation and for treatment of autoimmune diseases. The most troublesome side effect of CsA is renal injury. Acute CsA-induced nephrotoxicity is characterized by reduced renal blood flow (RBF) and glomerular filtration rate (GFR) due to afferent arteriole vasoconstriction. Annexin A1 (ANXA1) is a potent anti-inflammatory protein with protective effect in renal ischemia/reperfusion injury. Here we study the effects of ANXA1 treatment in an experimental model of acute CsA nephrotoxicity.
Salt-depleted rats were randomized to treatment with VH (vehicles 1 mL/kg body weight/day), ANXA1 (Ac2-26 peptide 1 mg/kg body weight/day intraperitoneally), CsA (20 mg/kg body weight/day subcutaneously) and CsA + ANXA1 (combination) for seven days. We compared renal function and hemodynamics, renal histopathology, renal tissue macrophage infiltration and renal ANXA1 expression between the four groups.
CsA significantly impaired GFR and RBF, caused tubular dilation and macrophage infiltration and increased ANXA1 renal tissue expression. Treatment with ANXA1 attenuated CSA-induced hemodynamic changes, tubular injury and macrophage infiltration.
ANXA1 treatment attenuated renal hemodynamic injury and inflammation in an acute CsA nephrotoxicity model.
环孢素（CsA）仍然是移植和治疗自身免疫性疾病的重要免疫抑制剂。CsA 最麻烦的副作用是肾损伤。急性 CsA 诱导的肾毒性的特征是由于入球小动脉收缩导致肾血流量（RBF）和肾小球滤过率（GFR）降低。膜联蛋白 A1（ANXA1）是一种具有抗炎作用的有效蛋白，在肾缺血/再灌注损伤中具有保护作用。在这里，我们研究了 ANXA1 治疗在急性 CsA 肾毒性实验模型中的作用。
盐耗竭大鼠随机分为 VH（载体 1ml/kg 体重/天）、ANXA1（Ac2-26 肽 1mg/kg 体重/天腹腔内注射）、CsA（20mg/kg 体重/天皮下注射）和 CsA+ANXA1（联合）治疗 7 天。我们比较了四组之间的肾功能和血液动力学、肾组织病理学、肾组织巨噬细胞浸润和肾 ANXA1 表达。
CsA 显著损害 GFR 和 RBF，导致肾小管扩张和巨噬细胞浸润，并增加肾组织 ANXA1 的表达。用 ANXA1 治疗可减轻 CSA 引起的血液动力学变化、肾小管损伤和巨噬细胞浸润。
ANXA1 治疗可减轻急性 CsA 肾毒性模型中的肾血流动力学损伤和炎症。
