School of Medicine, Guizhou University, Guiyang, Guizhou, China.
Department of Urology, Tongren City People's Hospital, Tongren, Guizhou, China.
Mol Cell Biochem. 2022 Jun;477(6):1873-1885. doi: 10.1007/s11010-022-04413-4. Epub 2022 Mar 26.
Renal ischemia-reperfusion (I/R) injury is one of the most common causes of chronic kidney disease (CKD). It brings unfavorable outcomes to the patients and leads to a considerable socioeconomic burden. The study of renal I/R injury is still one of the hot topics in the medical field. Ebselen is an organic selenide that attenuates I/R injury in various organs. However, its effect and related mechanism underlying renal I/R injury remains unclear. In this study, we established a rat model of renal I/R injury to study the preventive effect of ebselen on renal I/R injury and further explore the potential mechanism of its action. We found that ebselen pretreatment reduced renal dysfunction and tissue damage caused by renal I/R. In addition, ebselen enhanced autophagy and inhibited oxidative stress. Additionally, ebselen pretreatment activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The protective effect of ebselen was suppressed by autophagy inhibitor wortmannin. In conclusion, ebselen could ameliorate renal I/R injury, probably by enhancing autophagy, activating the Nrf2 signaling pathway, and reducing oxidative stress.
肾缺血再灌注(I/R)损伤是慢性肾脏病(CKD)最常见的原因之一。它给患者带来不良后果,并导致相当大的社会经济负担。肾 I/R 损伤的研究仍然是医学领域的热点之一。依布硒啉是一种有机硒化物,可减轻各种器官的 I/R 损伤。然而,其在肾 I/R 损伤中的作用及其相关机制尚不清楚。在这项研究中,我们建立了大鼠肾 I/R 损伤模型,研究依布硒啉对肾 I/R 损伤的预防作用,并进一步探讨其作用的潜在机制。我们发现,依布硒啉预处理可减轻肾 I/R 引起的肾功能障碍和组织损伤。此外,依布硒啉增强自噬并抑制氧化应激。此外,依布硒啉预处理激活了核因子红细胞 2 相关因子 2(Nrf2)信号通路。自噬抑制剂wortmannin 抑制了依布硒啉的保护作用。总之,依布硒啉可以改善肾 I/R 损伤,可能是通过增强自噬、激活 Nrf2 信号通路和减少氧化应激。