重组人促红细胞生成素减轻慢性环孢素肾病的间质炎症和纤维化
Attenuation of interstitial inflammation and fibrosis by recombinant human erythropoietin in chronic cyclosporine nephropathy.
作者信息
Lee Seung Hun, Li Can, Lim Sun Woo, Ahn Kyung Ohk, Choi Bum Soon, Kim Yong Soo, Moon In Sung, Kim Jin, Bang Byung Kee, Yang Chul Woo
机构信息
Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
出版信息
Am J Nephrol. 2005 Jan-Feb;25(1):64-76. doi: 10.1159/000084275. Epub 2005 Mar 2.
BACKGROUND
Evidence suggests that recombinant human erythropoietin (rHuEPO) protects neurons and cardiomyocytes from acute insults. We investigated the protective effect of rHuEPO on cyclosporine (CsA)-induced renal injury.
METHODS
CsA (15 mg/kg/day) was given to rats for 1 or 4 weeks, and rHuEPO was concurrently administered at a dose of 100 units/kg (thrice weekly). Effects of rHuEPO on CsA-induced renal injury were evaluated with tubulointerstitial fibrosis (TIF) score, macrophage infiltration, expression of proinflammatory and profibrotic cytokines, and apoptotic cell death.
RESULTS
Administration of rHuEPO decreased TIF score and the number of macrophages, which increased significantly in CsA-treated rat kidneys. At the molecular level, rHuEPO treatment decreased proinflammatory mediators (osteopontin and C-reactive protein) and profibrotic mediators (transforming growth factor-beta1 and transforming growth factor-beta1-inducible gene-h3). Increased apoptotic cell death in CsA-treated rat kidneys was significantly decreased with rHuEPO cotreatment, and apoptosis-related genes were regulated in favor of cell survival (increased Bcl-2 and suppressed caspase-3).
CONCLUSION
rHuEPO has a renoprotective effect against chronic CsA-induced renal injury.
背景
有证据表明，重组人促红细胞生成素（rHuEPO）可保护神经元和心肌细胞免受急性损伤。我们研究了rHuEPO对环孢素（CsA）诱导的肾损伤的保护作用。
方法
给大鼠注射CsA（15毫克/千克/天），持续1或4周，同时以100单位/千克的剂量（每周三次）注射rHuEPO。通过肾小管间质纤维化（TIF）评分、巨噬细胞浸润、促炎和促纤维化细胞因子的表达以及凋亡细胞死亡来评估rHuEPO对CsA诱导的肾损伤的影响。
结果
注射rHuEPO可降低TIF评分和巨噬细胞数量，而在CsA处理的大鼠肾脏中，这些指标显著增加。在分子水平上，rHuEPO处理可降低促炎介质（骨桥蛋白和C反应蛋白）和促纤维化介质（转化生长因子-β1和转化生长因子-β1诱导基因-h3）。rHuEPO联合处理可显著降低CsA处理的大鼠肾脏中增加的凋亡细胞死亡，并且凋亡相关基因的调节有利于细胞存活（Bcl-2增加，caspase-3受到抑制）。
结论
rHuEPO对慢性CsA诱导的肾损伤具有肾保护作用。
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