Nrf2/HO-1/NQO1 Pathway-Mediated Regulation of Mitophagy in Renal Ischemia-Reperfusion Injury
Abstract
Objective: To investigate the mechanism by which the nuclear factor
erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway mediates mitophagy to protect against renal ischemia-reperfusion injury (RIRI)Methods: A total of 40 rats were randomly divided into four groups. Ten rats
were assigned to the control group and were given normal saline. The remaining
30 rats were used to establish a RIRI model, with 28 rats successfully modeled.
These were then divided into three groups: the model group (n = 10), which received normal saline; the agonist group (n = 9), which received an Nrf2 agonist;
and the inhibitor group (n = 9), which received an Nrf2 inhibitor. After 14 days
of intervention, renal function (blood urea nitrogen (BUN) and serum creatinine
(Scr)), oxidative stress indicators (malondialdehyde (MDA) and superoxide dismutase (SOD)), expression levels of mitophagy-related proteins (BCL-2/BNIP3/
LC3-II), and expression levels of Nrf2, HO-1, and NQO1 were measured.Results: Compared with the control group, the model, agonist, and inhibitor
groups showed significantly increased levels of BUN, Scr and MDA, while the
levels of SOD, the expression of mitophagy-related proteins (Bnip3 and LC3-
II), and the mRNA and protein expression levels of Nrf2, HO-1, and NQO1 were
significantly decreased (P < 0.05). Compared with the model group, the agonist
group showed significantly decreased BUN, Scr, and MDA levels, and significantly increased SOD levels, BNIP3 and LC3-II protein expression, as well as
mRNA and protein expression of Nrf2, HO-1, and NQO1 (P < 0.05); whereas
the inhibitor group showed increased BUN, Scr, and MDA levels and decreased
SOD levels, BNIP3 and LC3-II protein expression, and Nrf2, HO-1, and NQO1
mRNA and protein levels (P < 0.05). Compared with the agonist group, the inhibitor group exhibited significantly higher BUN, Scr, and MDA levels and lower
SOD levels, Bnip3 and LC3-II protein expression, and Nrf2, HO-1, and NQO1mRNA and protein expression (P < 0.05)
Copyright (c) 2025 Zexin wang, Jinghui Fan, Xing Li, Zelin Guo, Fan Cheng
This work is licensed under a Creative Commons Attribution 4.0 International License.
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