Mechanism of Propofol Attenuating Brain Injury Induced by Sepsis in Mice

Abstract

Objectives: The treatment of sepsis has received widespread attention in recent years, but morbidity and mortality rates are still increasing in clinical practice. This project aims to evaluate the outcome of propofol (PF) on brain injury induced by sepsis and explore its potential mechanism. Methods: A total of 48 C57BL/6 mice were randomly divided into four subgroups, each containing 12 mice: a control (Con) subgroup, a sepsis lipopolysaccharide (LPS) subgroup, a fat emulsion (LPS + Lip) subgroup, and a propofol (LPS + PF) subgroup. The model was successfully built, and the pathological changes of brain tissue were evaluated using Hematoxylin eosin (HE) staining. Inflammatory indicators, including S-100β protein (S100-β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and neuron specific enolase (NSE), were measured using Enzyme-Linked Immunosorbent Assay (ELISA). The lactic acid (LA) concentration in brain tissue was measured using a colorimetric quantitative method. Acetylcholinesterase (Ach-E) activity was measured using an ELISA kit. Inflammation-related proteins, including Caspase-1, NOD-like receptor family pyrin domain-containing 3 (NLRP3), and Heme oxygenase-1 (HO-1) concentrations, were measured by western blot. The reactive oxygen species (ROS) concentration was measured by immunofluorescence. Oxidative stress-related indicators, including malondialdehyde (MDA), nitric oxide (NO), glutathione peroxidase (GSH) and superoxide dismutase (SOD) concentrations were measured using a biochemical kit. Results: This study found that the injury to the hippocampal Cornu Ammonis Area 1 (CA1) in the LPS subgroup was severe, with a decrease in the neurobehavioral score (p < 0.001). Additionally, the concentrations of S100-β, LA, IL-6, TNF-α, NSE, ROS, MDA and NO, as well as the activity of Acetylcholinesterase (Ach-E), were significantly increased (p < 0.001). On the other hand, the concentrations of GSH and SOD were significantly decreased (p < 0.001), while the concentrations of Caspase-1 and NLRP3 were increased (p < 0.001), and the mRNA and protein levels of Nuclear factor erythroid2-related factor 2 (Nrf2) and HO-1 were significantly decreased compared to the Con subgroup (p < 0.001). However, after the intervention of PF, the above results were reversed (p < 0.01). Conclusions: PF has been shown to significantly mitigate sepsis-induced brain injury in mice. The underlying mechanism of this effect may be related to the Nrf2/HO-1 pathway.