Nrf2通过Nrf2/TrxR2信号通路对慢性间歇性缺氧所致肾损伤的保护作用
Nrf2 protects against renal injury induced by chronic intermittent hypoxia via Nrf2/TrxR2 signaling pathway.
文献信息
| PMID | 42956563 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Xiucui Li |
| 作者单位 | Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China. |
| 期刊 | Sleep medicine |
| SCI 分区 | Q1 |
| IF | 4.5 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 鼻科 |
中文摘要
背景： 阻塞性睡眠呼吸暂停低通气综合征（OSAHS）以慢性间歇性缺氧（CIH）为特征，与儿童人群的肾损伤相关。核因子E2相关因子2（Nrf2）已知对氧化应激具有保护作用，但其在CIH所致肾损伤中的作用仍不清楚。
目的： 本研究旨在探讨Nrf2是否对CIH所致肾损伤具有保护作用，并探索Nrf2/TrxR2信号通路的参与。
方法： 将C57BL/6小鼠暴露于CIH，并给予Nrf2激动剂萝卜硫素（SFN）或抑制剂ATRA处理。同时，将HK-2肾小管细胞置于CIH条件下，并进行Nrf2或TrxR2 siRNA敲低。评估肾功能、组织病理学、氧化应激标志物、Nrf2核转位及下游抗氧化蛋白表达。
关键结果： CIH暴露4周显著损害肾功能，表现为血清肌酐、血尿素氮和尿β2-微球蛋白水平升高。组织学上，CIH引起肾小管上皮细胞肿胀、管腔狭窄和间质纤维化。Nrf2激活改善了这些功能和结构异常，而Nrf2抑制则加重了这些异常。机制上，Nrf2激活增强了其核转位并上调TrxR2表达，同时伴有超氧化物歧化酶活性增加和丙二醛水平降低。
结论： Nrf2通过Nrf2/TrxR2信号通路抑制氧化应激，从而减轻CIH所致肾损伤，提示Nrf2是OSAHS相关肾功能障碍的潜在治疗靶点。
英文摘要
BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS), characterized by chronic intermittent hypoxia (CIH), is associated with renal injury in pediatric populations. Nuclear factor E2-related factor 2 (Nrf2) is known to exert protective effects against oxidative stress, yet its role in CIH-induced renal damage remains unclear.
AIMS: This study aims to investigate whether Nrf2 protects against CIH-induced renal injury and to explore the involvement of the Nrf2/TrxR2 signaling pathway.
METHODS: C57BL/6 mice were exposed to CIH and treated with the Nrf2 agonist sulforaphane (SFN) or the inhibitor ATRA. In parallel, HK-2 renal tubular cells were subjected to CIH with Nrf2 or TrxR2 siRNA knockdown. Renal function, histopathology, oxidative stress markers, Nrf2 nuclear translocation, and downstream antioxidant protein expression were evaluated.
KEY RESULTS: Four weeks of CIH exposure significantly impaired renal function, as evidenced by elevated serum creatinine, blood urea nitrogen, and urinary β2-microglobulin levels. Histologically, CIH caused tubular epithelial cell swelling, luminal narrowing, and interstitial fibrosis. Nrf2 activation ameliorated these functional and structural abnormalities, while Nrf2 inhibition aggravated them. Mechanistically, Nrf2 activation enhanced its nuclear translocation and upregulated TrxR2 expression, accompanied by increased superoxide dismutase activity and decreased malondialdehyde levels.
CONCLUSIONS: Nrf2 alleviates CIH-induced renal injury by suppressing oxidative stress through the Nrf2/TrxR2 signaling pathway, highlighting Nrf2 as a potential therapeutic target for OSAHS-related renal dysfunction.