Dexmedetomidine Alleviates Ferroptosis Induced by Sepsis-Induced Renal Injury by Activating Keap1-Nrf2 Signaling Pathway.

Abstract

Background: The purpose of this study was to investigate the protective effect of dexmedetomidine (DEX) on sep¬sis-induced acute kidney injury (AKI) and its possible mechanisms.

Methods: A total of 40 mice were randomly divided into the control group (C group), lipopolysaccharide treatment group (LPS group), LPS+DEX group, and ferrostatin-1 group (LPS+Fer-1 group). Mice in the LPS group were intraperitoneally injected with LPS (10 mg/kg), while mice in the LPS+DEX and LPS+Fer-1 groups were intraperitoneally injected with Dex (30 μg/kg) and Fer-1 (10 mg/kg), 1 hour before LPS injection, respectively. Mice in the control group were infused with the same volume of saline. Serum creatinine (SCr), blood urea nitrogen (BUN) and the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (T-AOC) in renal tissue were measured. HE staining was used to evaluate the degree of kidney tissue injury. Immunohistochemistry and western blot were used to detect the protein expressions of FTH, TFR, Keap1, and Nrf2 in kidney tissue.

Results: Compared with the control group, the serum levels of SCr and BUN were significantly increased, the levels of SOD and T-AOC in the kidney were decreased, the MDA level and renal injury score were increased, the expression of FTH and Nrf2 protein was reduced, and the expression of TFR and Keap1 protein was increased in the LPS group (p < 0.05). Compared with the LPS group, the serum levels of SCr and BUN were significantly de-creased, the levels of SOD and T-AOC in the kidney were increased, the MDA level and renal injury score were decreased, the expression of FTH and Nrf2 protein was increased, and the expression of TFR and Keap1 protein was decreased in the LPS+DEX group (p < 0.05).

Conclusions: Dex can alleviate sepsis-associated acute kidney injury by activating the Keap1/Nrf2 pathway.