The purpose of the work was to investigate mechanisms of erythropoietin-induced protection and accelerated recovery of kidneys and ureters from obstructive injury. Unilateral ureteral obstruction was established for 24, 48, and 72 h in C57BL/6 mice using a non-traumatic micro-clip followed by the microscopic quantification of ureteral peristalsis pre- and post-obstruction. Expression of erythropoietin, erythropoietin receptor, β-common receptor, and downstream apoptosis-related markers was assessed by RT-PCR and immunohistochemistry in ureters and kidneys and compared to the respective organs on the contralateral side within each animal. Expression of genes in kidneys and ureters from mice treated with 20 IU of erythropoietin daily for 72 h prior to obstruction was compared to that of untreated mice following obstruction. Apoptosis in ureteral tissues after 72-h obstruction was assessed via TUNEL assay. Ureteral obstruction increased apoptosis in affected ureters, with peristaltic function halted following all periods of obstruction. Erythropoietin treatment suppressed apoptosis in obstructed tissues and increased the percentage of mice retaining ureteral function immediately following obstruction reversal. Erythropoietin, erythropoietin receptor, Bcl-2, and Bcl-xl mRNA expression were down-regulated, while phospho-Nf-ĸb p65 was up-regulated in ureteral epithelia following obstruction. Erythropoietin treatment induced anti-apoptotic signaling via down-regulated Bax mRNA expression and abrogated phospho-Nf-ĸb p65. Erythropoietin-induced protection of ureteral function and accelerated recovery post-obstruction removal is mediated via anti-apoptotic mechanisms. Ureteral function is disrupted even following obstruction removal, negatively affecting renal function due to delayed recovery. Thus, our results represent a potential target for the development of safe therapeutic agents aimed at improving functional recovery from obstructive injury.

中文翻译：

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促红细胞生成素通过抗凋亡机制促进小鼠单侧输尿管梗阻的功能恢复。


这项工作的目的是研究促红细胞生成素诱导的保护机制以及加速肾脏和输尿管从阻塞性损伤中恢复的机制。使用非创伤性微夹在 C57BL/6 小鼠中建立单侧输尿管梗阻 24、48 和 72 小时，然后对梗阻前后输尿管蠕动进行显微量化。通过 RT-PCR 和免疫组织化学评估每只动物输尿管和肾脏中促红细胞生成素、促红细胞生成素受体、β-共同受体和下游凋亡相关标志物的表达，并与对侧相应器官进行比较。将梗阻前每天用 20 IU 促红细胞生成素治疗 72 小时的小鼠的肾脏和输尿管基因表达与梗阻后未治疗的小鼠进行比较。通过 TUNEL 测定评估阻塞 72 小时后输尿管组织的细胞凋亡。输尿管梗阻增加受影响输尿管的细胞凋亡，在所有梗阻期间蠕动功能停止。促红细胞生成素治疗抑制了梗阻组织的细胞凋亡，并增加了梗阻逆转后立即保留输尿管功能的小鼠的百分比。梗阻后输尿管上皮中促红细胞生成素、促红细胞生成素受体、Bcl-2 和 Bcl-xl mRNA 表达下调，而磷酸-Nf-ĸb p65 表达上调。促红细胞生成素治疗通过下调 Bax mRNA 表达和废除磷酸-Nf-ĸb p65 诱导抗凋亡信号传导。促红细胞生成素诱导的输尿管功能保护和梗阻清除后的加速恢复是通过抗凋亡机制介导的。 即使在梗阻清除后，输尿管功能也会受到干扰，由于恢复延迟而对肾功能产生负面影响。因此，我们的结果代表了开发旨在改善阻塞性损伤功能恢复的安全治疗剂的潜在目标。