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依布硒啉通过增强自噬减轻大鼠肾缺血再灌注损伤。

Ebselen ameliorates renal ischemia-reperfusion injury via enhancing autophagy in rats.

机构信息

School of Medicine, Guizhou University, Guiyang, Guizhou, China.

Department of Urology, Tongren City People's Hospital, Tongren, Guizhou, China.

出版信息

Mol Cell Biochem. 2022 Jun;477(6):1873-1885. doi: 10.1007/s11010-022-04413-4. Epub 2022 Mar 26.

Abstract

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.

摘要

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。

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