Eren Zehra, Günal Mehmet Yalçın, Arı Elif, Çoban Jale, Çakalağaoğlu Fulya, Çağlayan Burak, Beker Mustafa Çağlar, Akdeniz Tuba, Yanıkkaya Gülderen, Kılıç Ertuğrul, Kantarcı Gülçin
Department of Physiology, Medipol University, Medical Faculty, Istanbul, Turkey.
Nephron. 2016;132(4):292-300. doi: 10.1159/000444649. Epub 2016 Mar 4.
This study aimed at investigating the possible protective effect of erythropoietin beta on experimental diabetic nephropathy (DN) model in rats.
Sprague Dawley rats (n = 32) were allocated into 4 equal groups of 8 each, the control (Group C), diabetes (Group D), erythropoietin beta (Group E), and erythropoietin beta treated DN (Group E + D) groups. Streptozocin (65 mg/kg) was used to induce diabetes in 10-week old rats. Erythropoietin beta was given intraperitoneally at a dose of 500 IU/kg/3 days of a week for 12 weeks. Renal function parameters, intrarenal levels and activities of oxidative stress biomarkers, serum inflammatory parameters and kidney histology were determined.
Group E + D had lower mean albumin-to-creatinine ratio (p < 0.001) as well as higher creatinine clearance (p = 0.035) than the diabetic rats (Group D). Intrarenal malondialdehyde levels were significantly lower (p = 0.004); glutathione (GSH) levels (p = 0.003), GSH peroxidase (p = 0.004) and superoxide dismutase (p < 0.005) activities of renal tissue were significantly higher in Group E + D than in Group D. The mean serum levels of interleukin-4 (p < 0.005), interleukin 1 beta (p = 0.012), interferon gamma (p = 0.018) and tumor necrosis factor alpha (p < 0.005) were significantly lower; serum levels of monocyte chemoattractant protein 1 (p = 0.018) was significantly higher in Group E + D when compared to Group D. The mean scores of tubulointerstitial inflammation (p = 0.004), tubular injury (p = 0.013) and interstitial fibrosis (p = 0.003) were also lower in Group E + D when compared to Group D.
Our data seem to suggest a potential role of erythropoietin beta for reducing the progression of DN in an experimental rat model. This protective effect is, in part, attributable to the suppression of the inflammatory response and oxidative damage.
本研究旨在探讨促红细胞生成素β对大鼠实验性糖尿病肾病（DN）模型的可能保护作用。
将32只Sprague Dawley大鼠平均分为4组，每组8只，分别为对照组（C组）、糖尿病组（D组）、促红细胞生成素β组（E组）和促红细胞生成素β治疗的DN组（E + D组）。采用链脲佐菌素（65 mg/kg）诱导10周龄大鼠患糖尿病。促红细胞生成素β以500 IU/kg/周3天的剂量腹腔注射，持续12周。测定肾功能参数、肾内氧化应激生物标志物水平和活性、血清炎症参数及肾脏组织学。
与糖尿病大鼠（D组）相比，E + D组的平均白蛋白与肌酐比值更低（p < 0.001），肌酐清除率更高（p = 0.035）。E + D组肾内丙二醛水平显著更低（p = 0.004）；肾组织中谷胱甘肽（GSH）水平（p = 0.003）、GSH过氧化物酶（p = 0.004）和超氧化物歧化酶活性（p < 0.005）显著高于D组。E + D组白细胞介素-4（p < 0.005）、白细胞介素1β（p = 0.012）、干扰素γ（p = 0.018）和肿瘤坏死因子α（p < 0.005）的平均血清水平显著更低；与D组相比，E + D组单核细胞趋化蛋白1的血清水平显著更高（p = 0.018）。与D组相比，E + D组肾小管间质炎症（p = 0.004）、肾小管损伤（p = 0.013）和间质纤维化（p = 0.003）的平均评分也更低。
我们的数据似乎表明促红细胞生成素β在实验性大鼠模型中对减缓DN进展具有潜在作用。这种保护作用部分归因于对炎症反应和氧化损伤的抑制。
