Chang Yoon-Kyung, Choi Dae Eun, Na Ki-Ryang, Lee Sang-Ju, Suh Kwang-Sun, Kim Suk Young, Shin Young-Tai, Lee Kang Wook
Department of Nephrology, Catholic University Daejeon St. Mary Hospital, Daejeon, Republic of Korea.
J Urol. 2009 Mar;181(3):1434-43. doi: 10.1016/j.juro.2008.10.105. Epub 2009 Jan 20.
Erythropoietin was recently shown to exert important cytoprotective and anti-apoptotic effects in injury models of the brain, heart and kidney. We examined whether erythropoietin also attenuates renal injury in a rat model of unilateral ureteral obstruction via anti-apoptotic and anti-inflammatory actions.
We divided Sprague-Dawley rats (Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea) into 4 groups, including 1-vehicle treated with sham operation, 2-vehicle treated with unilateral ureteral obstruction for 3 days, 3-erythropoietin treatment with sham operation and 4-erythropoietin treatment for unilateral ureteral obstruction for 3 days. The erythropoietin treatment dose was 3,000 IU/kg per day intraperitoneally, administered daily. We compared competitive reverse transcriptase-polymerase chain reaction data on transforming growth factor-beta, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, osteopontin, Fas and Bcl-2. Furthermore, we examined Western blots for caspase-3 and light microscopy findings with hematoxylin and eosin staining. We applied immunohistochemistry for transforming growth factor-beta, ED-1 and caspase-3, and TUNEL in each group.
Transforming growth factor-beta, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, osteopontin and Fas mRNA levels in the erythropoietin treated, unilateral ureteral obstruction group were significantly lower than in the obstruction only group. The Bcl-2 mRNA level in the erythropoietin treated obstruction group was significantly higher than in the obstruction only group. Caspase-3 activity in the erythropoietin treated obstruction group was significantly lower than in the obstruction only group. On light microscopy interstitially infiltrated inflammatory cells were significantly decreased in the erythropoietin treated obstruction group compared to the obstruction only group. On immunohistochemistry the erythropoietin treated obstruction group showed significantly fewer reactions for transforming growth factor-beta, ED-1 and caspase-3 compared to the obstruction only group. Erythropoietin treatment in rats with unilateral ureteral obstruction significantly decreased the number of TUNEL positive cells.
Erythropoietin exerts renoprotective effects in an experimental unilateral ureteral obstruction rat model via anti-apoptotic and anti-inflammatory actions.
最近研究表明，促红细胞生成素在脑、心脏和肾脏损伤模型中发挥重要的细胞保护和抗凋亡作用。我们研究了促红细胞生成素是否也通过抗凋亡和抗炎作用减轻单侧输尿管梗阻大鼠模型中的肾损伤。
我们将Sprague-Dawley大鼠（韩国大田市韩国生物科学与生物技术研究所）分为4组，包括1-假手术组给予溶剂对照，2-单侧输尿管梗阻3天组给予溶剂对照，3-假手术组给予促红细胞生成素治疗，4-单侧输尿管梗阻3天组给予促红细胞生成素治疗。促红细胞生成素治疗剂量为每天3000 IU/kg，腹腔内注射，每日给药。我们比较了转化生长因子-β、肿瘤坏死因子-α、单核细胞趋化蛋白-1、骨桥蛋白、Fas和Bcl-2的竞争性逆转录聚合酶链反应数据。此外，我们检测了caspase-3的蛋白质免疫印迹以及苏木精和伊红染色的光学显微镜检查结果。我们对每组进行了转化生长因子-β、ED-1和caspase-3的免疫组织化学检测以及TUNEL检测。
促红细胞生成素治疗的单侧输尿管梗阻组中，转化生长因子-β、肿瘤坏死因子-α、单核细胞趋化蛋白-1、骨桥蛋白和Fas mRNA水平显著低于单纯梗阻组。促红细胞生成素治疗的梗阻组中Bcl-2 mRNA水平显著高于单纯梗阻组。促红细胞生成素治疗的梗阻组中caspase-3活性显著低于单纯梗阻组。光学显微镜检查显示，与单纯梗阻组相比，促红细胞生成素治疗的梗阻组间质浸润的炎性细胞显著减少。免疫组织化学检测显示，与单纯梗阻组相比，促红细胞生成素治疗的梗阻组转化生长因子-β、ED-1和caspase-3的反应显著减少。促红细胞生成素治疗单侧输尿管梗阻大鼠可显著减少TUNEL阳性细胞数量。
促红细胞生成素通过抗凋亡和抗炎作用在实验性单侧输尿管梗阻大鼠模型中发挥肾保护作用。
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