Pharmacological Inhibition of the HSPB1-NF-κB Axis Alleviates Brain Injury in a Rat Veno-Venous Extracorporeal Membrane Oxygenation Model.

Abstract

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a critical intervention for acute respiratory distress syndrome, yet its application is frequently associated with brain injury, which significantly impacts patient prognosis. Heat shock protein B1 (HSPB1) is strongly involved in neuroinflammatory responses; however, its role in brain injury related to VV-ECMO remains to be elucidated. We established a VV-ECMO rat model to evaluate the neuroprotective effects of inhibiting the HSPB1-NF-κB axis (HSPB1 inhibitor J2, 1 mg/kg, ip). Serum levels of the brain injury biomarkers S100β and NSE were measured using ELISA, histopathological features of brain injury were evaluated by hematoxylin and eosin staining, and microglial and astrocyte activation was assessed through immunofluorescence staining. Western blotting and real-time quantitative PCR were employed to examine the effects of J2 on the expression of Il-1β, Il-6, Tnf-α, and the activation of the NF-κB signaling pathway. We observed that, following the establishment of the VV-ECMO model, brain injury was associated with an increase in neuroinflammatory responses, with both HSPB1 expression and the NF-κB signaling pathway being significantly upregulated. Administration of J2 alleviated brain injury, as indicated by reduced activation of microglia and astrocytes, decreased levels of Il-1β, Il-6, and Tnf-α, and significant suppression of the NF-κB signaling pathway. Our findings suggest that the HSPB1-NF-κB axis serves as a key mediator of neuroinflammation during VV-ECMO, providing important insights into the molecular mechanisms underlying VV-ECMO-related brain injury and offering a rationale for future studies.