Early PEG-bHb resuscitation for hemorrhagic shock: Attenuation of acute kidney injury via the Nrf2/HO-1 pathway.
Yu Hang, You Guoxing, Chen Yuzhi, Li Weidan, Zhang Xiaoyong, Zhou Hong, Zhao Lian, Wang Ying
Abstract
BACKGROUND: Hemorrhagic shock (HS) is a major cause of traumatic death, strongly influenced by resuscitation timing. This study explored the protective effects and mechanisms of early polyethylene glycol-conjugated bovine hemoglobin (PEG-bHb) resuscitation in HS treatment. METHODS: Following subjecting HS, rats received PEG-bHb resuscitation at 0-30 min (R_30), 30-60 min (R_60), or 60-90 min (R_90), or conventional crystalloid-colloid solution as control. Hemodynamic, acid-base, and microcirculatory parameters, survival time, renal histopathology, and pimonidazole hypoxia staining were assessed to verify the resuscitation effect. Renal transcriptomic profiling was performed, followed by validation of inflammation, oxidative stress, apoptosis, mitochondrial morphology, and Nrf2/HO-1 pathway activation. The Nrf2 inhibitor ML385 was used to confirm pathway involvement. RESULTS: All PEG-bHb groups showed restoration of hemodynamic, acid-base, and microcirculatory parameters, yet R_30 and R_60 significantly prolonged survival (27.59 h, 28.03 h) versus HES (<4 h). Histopathological and pimonidazole hypoxia staining showed markedly attenuated renal injury and reduced renal tissue hypoxia after early resuscitation. Transcriptomic and validation results revealed that R_30 suppressed renal inflammation, oxidative stress, and apoptosis, restored mitochondrial morphology, and activated the Nrf2/HO-1 pathway. Nrf2 inhibition by ML385 abolished these protective effects. CONCLUSIONS: Early PEG-bHb resuscitation ameliorates HS-induced acute kidney injury and improves survival by activating the Nrf2/HO-1 signaling pathway.
Key Findings
- Early PEG-bHb resuscitation (within 60 minutes) significantly prolongs survival in hemorrhagic shock compared to conventional treatment.
- Early PEG-bHb resuscitation attenuates acute kidney injury by reducing renal inflammation, oxidative stress, apoptosis, and tissue hypoxia.
- The protective effects of PEG-bHb are mediated via activation of the Nrf2/HO-1 signaling pathway, and inhibition of Nrf2 abolishes these benefits.
Clinical Significance
Early administration of PEG-bHb in hemorrhagic shock patients may improve survival and reduce acute kidney injury by activating antioxidant defense pathways, highlighting a potential therapeutic strategy targeting oxidative stress mechanisms.
Citation
Yu Hang, You Guoxing, Chen Yuzhiet al.. Early PEG-bHb resuscitation for hemorrhagic shock: Attenuation of acute kidney injury via the Nrf2/HO-1 pathway. Life sciences. 2026-Oct-24.