Effect of Celastrol on sevoflurane-induced neurotoxicity in elderly rats by regulating the Fas/FasL signaling pathway
LI Yuan
YAO Shuo
DUAN Chao
Abstract：Objective To investigate the effect of Celastrol(Cel)on sevoflurane-induced neurotoxicity in elderly rats and its related mechanism.Methods A sevoflurane induction model in rats was established,and all rats were randomly assigned into control group(group C),Model group,Cel group,Cel+Ad-NC group,and Cel+Ad-Fas group.Doppler ultrasound was applied to detect arterial hemodynamic indicators.Water maze test was applied to evaluate spatial learning and memory abilities.Open field experiment was applied to evaluate autonomous activity and anxiety state.Synaptic and vesicular areas of hippocampal neurons were observed and counted under an electron microscope.The terminal deoxynucleotidyl transferase dUTP nick end-labeling(TUNEL)staining was applied to measure the apoptosis rate of hippocampal neurons.Western blot was applied to detect the protein levels of fatty acid synthase(Fas)and fatty acid synthase ligand(FasL)in rat hippocampus.Results Compared with group C,the peak systolic velocity(PSV),end-diastolic velocity(EDV),resistive index(RI),spatial learning ability,and synaptic and vesicular areas of rats in Model group significantly decreased,while the degree of spontaneous activity and anxiety,the rate of neuronal apoptosis,and the protein levels of Fas and FasL significantly increased(P＜0.05).Compared with those of the Model group,the PSV,EDV,RI,spatial learning ability,synaptic and vesicular areas of rats in Cel group significantly increased,while the degree of spontaneous activity and anxiety,the rate of neuronal apoptosis,and the protein levels of Fas and FasL significantly decreased(P＜0.05).Compared with those of the Cel+Ad-NC group,the PSV,EDV,RI,spatial learning ability,synaptic and vesicular areas of rats in Cel+Ad-Fas group significantly decreased,while the degree of spontaneous activity and anxiety,the rate of neuronal apoptosis,and the protein levels of Fas and FasL significantly increased(P＜0.05).Conclusion Cel may improve sevoflurane-induced neurotoxicity in elderly rats by down-regulating the Fas/FasL signaling pathway.
Keywords：Celastrolsevofluraneelderly ratsneurotoxicityfatty acid synthase/fatty acid synthase ligand signaling pathway
Publication Date：2025-03-26
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 396-400,405 )