PROTECTIVE EFFECT OF REMIMAZOLAM ON CEREBRAL NERVES IN A RAT MODEL OF CEREBRAL ISCHEMIA/REPERFUSION INJURY AND ITS MECHANISM

Abstract

Objective To investigate the protective effect of remimazolam on cerebral nerves in a rat model of cerebral ischemia/reperfusion injury and its mechanism. Methods A total of 50 male Sprague-Dawley rats were randomly divided into sham-operation group (Sham group), cerebral ischemia/reperfusion group (I/R group), I/R+remimazolam (RE) group, I/R+RE+LY294002 (LY) group, and I/R+LY group. Neurological deficit score was used to evaluate the degree of neurological dysfunction. After arterial blood samples and brain tissue pathological sections were collected from the rats in each group, 2,3,5-trip-henyltetrazolium chloride staining was performed for the brain tissue sections to calculate cerebral infarct volume ratio; ELISA was used to measure the serum levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α); Western blotting was used to measure the relative expression levels of protein kinase B (AKT), phosphorylated AKT (p-AKT), nuclear factor-kappa B p65 (NF-κB p65), and phosphorylated NF-κB p65 (p-NF-κB p65) in brain tissue, and then immunofluorescence assay was used to measure the expression level of p-NF-κB p65 inside and outside the nucleus of cells in brain tissue. Results There were significant differences between these groups in cerebral infarct volume ratio, neurological deficit score, the serum levels of IL-6, IL-1β, and TNF-α, the relative expression levels of p-AKT and p-NF-κB p65, p-AKT/AKT ratio, and p-NF-κB p65/NF-κB p65 ratio (F=72.41-654.90,P<0.05). Compared with the Sham group, the I/R group had significant increases in cerebral infarct volume ratio, neurological deficit score, the serum levels of IL-6, IL-1β, and TNF-α, the relative expression level of p-NF-κB p65 in brain tissue, and p-NF-κB p65/NF-κB p65 ratio (P<0.05) and significant reductions in the relative expression level of p-AKT in brain tissue and p-AKT/AKT ratio (P<0.05), and immunofluorescence assay showed a significant increase in the nuclear translocation of p-NF-κB p65 in brain tissue. Compared with the I/R group, the I/R+RE+LY group, and the I/R+LY group, the I/R+RE group had significant reductions in cerebral infarct volume ratio, neurological deficit score, the serum levels of IL-6, IL-1β, and TNF-α, the relative expression level of p-NF-κB p65 in brain tissue, and p-NF-κB p65/NF-κB p65 ratio (P<0.05) and significant increases in the relative expression level of p-AKT in brain tissue and p-AKT/AKT ratio (P<0.05), and immunofluorescence assay showed a significant reduction in the nuclear translocation of p-NF-κB p65 in brain tissue. Conclusion Remimazolam exerts a protective effect on cerebral nerves by alleviating inflammatory response caused by brain I/R injury, possibly by regulating the AKT/NF-κB signaling pathway.

Keywords

• benzodiazepines|reperfusion injury|brain ischemia|nf-kappa b|proto-oncogene proteins c-akt|signal transduction|cytokines|inflammation