Nrf2 protects against renal injury induced by chronic intermittent hypoxia via Nrf2/TrxR2 signaling pathway

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.

This study aims to investigate whether Nrf2 protects against CIH-induced renal injury and to explore the involvement of the Nrf2/TrxR2 signaling pathway.

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.

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.

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.