Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Poorsina Ave, Tehran, Iran.
Research and Clinical Center for Infertility, Yazd Rreproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Mol Biol Rep. 2024 Aug 19;51(1):916. doi: 10.1007/s11033-024-09824-8.
In end stage renal disease )ESRD(, reduced EPO production resulted in decreased oxygen diffusion that cause Hypoxia-inducible factors (HIFs) stabilization. The mechanism of beneficial effects of HS in chronic kidney disease (CKD) is the aim of the present study to examine the effects of the HS donor sodium hydrosulfide (NaHS) on renal function parameters, oxidative stress indices and expression levels of HIF-2α gene and erythropoietin protein in 5/6 nephrectomy-induced chronic renal failure in rats.
Male rats were assigned into 3 groups (n = 8): Sham, CKD and NaHS groups. In the CKD group, 5/6 nephrectomy was performed. In the sham group, rats were anesthetized but 5/6 nephrectomy was not induced. In the NaHS group, 30 µmol/L of NaHS in drinking water for 8 weeks was adminstrated 4 weeks after 5/6 nephrectomy induction. At the end of the 12 week, blood and renal tissues were taken to evaluate renal function parameters, oxidative stress indices and expression levels of HIF-2α gene and erythropoietin protein.
The induction of 5/6 nephrectomy significantly caused renal dysfunction, oxidative stress, increased HIF-2α gene expression and decreased erythropoietin levels in renal tissue samples. NaHS administration resulted in a marked improvement in renal function and oxidative stress indicators, a marked reduction in HIF-2α gene expression as well as an increase in erythropoietin protein levels in comparison with the CKD group.
In this study, regional hypoxia and oxidative stress in CKD, may cause the stabilization of the HIFs complexes, although erythropoietin synthesis was not increased due to destructive effects of CKD on the kidney tissues. Administration of NaHS caused up-regulating HIF-erythropoietin signaling pathway.
在终末期肾脏疾病（ESRD）中，EPO 产生减少导致氧气扩散减少，从而导致缺氧诱导因子（HIFs）稳定。HS 在慢性肾脏病（CKD）中的有益作用机制是本研究的目的，旨在研究 HS 供体硫氢化钠（NaHS）对 5/6 肾切除诱导的慢性肾衰竭大鼠肾功能参数、氧化应激指标以及 HIF-2α 基因和促红细胞生成素蛋白表达水平的影响。
雄性大鼠被分为 3 组（n = 8）：假手术组、CKD 组和 NaHS 组。在 CKD 组中，进行 5/6 肾切除术。在假手术组中，大鼠被麻醉但未进行 5/6 肾切除术。在 NaHS 组中，在 5/6 肾切除术后 4 周开始给予 30 µmol/L 的 NaHS 饮用水 8 周。在第 12 周末，采集血液和肾脏组织，以评估肾功能参数、氧化应激指标以及 HIF-2α 基因和促红细胞生成素蛋白的表达水平。
5/6 肾切除术的诱导显著导致肾功能障碍、氧化应激、HIF-2α 基因表达增加和肾脏组织中促红细胞生成素水平降低。与 CKD 组相比，NaHS 给药导致肾功能和氧化应激指标显著改善，HIF-2α 基因表达显著降低，促红细胞生成素蛋白水平升高。
在这项研究中，CKD 中的局部缺氧和氧化应激可能导致 HIFs 复合物的稳定，尽管由于 CKD 对肾脏组织的破坏作用，促红细胞生成素的合成没有增加。NaHS 的给药导致 HIF-促红细胞生成素信号通路的上调。
