Protective effect of oxymatrine on brain injury in rats with acute carbon monoxide poisoning and the analysis of its potential mechanism

GAO Ying; ZHANG Junying; FANG Pingping; LIU Yangang; ZHAO Dongxia

doi:10.13431/j.cnki.immunol.j.20260015

Abstract：Objective To investigate the protective effects and potential mechanisms of oxymatrine(OMT)on brain injury in rats with acute carbon monoxide(CO)poisoning.Methods One hundred healthy adult male Sprague-Dawley rats were selected and adapted to standard laboratory conditions with natural light cycles and free access to water and food.On day 8 of feeding,they were randomly divided into four groups:control group(NC group),acute CO poisoning model group(CO group),acute CO poisoning model supplemented with OMT treatment group(OMT group),and acute CO poisoning model combined with OMT and silent information regulator 2 homolog(SIRT1)inhibitor treatment group(OMT+EX527 group),with 25 rats in each group.An acute CO poisoning model was established by CO gas inhalation.The OMT group received OMT at 200 mg/kg via gastric intubation,while the OMT+EX527 group received OMT at 200 mg/kg and SIRT1 inhibitor EX527 at 1 mg/kg via gastric intubation.The learning and memory abilities of rats in each group were evaluated through the Morris water maze test.Brain tissue samples were prepared and stained with HE to examine the morphology of brain tissues in each group.TUNEL staining was performed to detect apoptosis in brain cells of each group,and transmission electron microscopy was used to observe the ultrastructure of neurons in each group.Flow cytometry was employed to measure mitochondrial membrane potential in each group.Reactive oxygen species(ROS)levels in hippocampal tissues were determined using a ROS assay kit.Western blot analysis was conducted to assess the expression of SIRT1,FOXO1,Nrf-2,and Bcl-2 proteins in hippocampal tissues of each group.Results Compared with the CO group,the OMT group exhibited a shortened latency period for escape and a significantly increased number of platform crossings(P＜0.01).Compared with the CO group and OMT+EX527 group,the morphological structure of brain tissue cells in the OMT group was improved,while the rate of TUNEL-positive cells in the OMT group was reduced(P＜0.01).Compared with the CO group and OMT+EX527 group,the average fluorescence intensity of neurons in the hippocampus of the OMT group was increased(P＜0.01),while the ROS level in the hippocampal tissues of the OMT group was decreased(P＜0.01).Compared with the CO group,the expression levels of SIRT1,FOXO1,Nrf-2,and Bcl-2 proteins in hippocampal tissues of the OMT group were elevated(P＜0.05).Conclusion OMT may protect against acute CO-induced brain injury by activating SIRT1/FOXO1 signaling pathway,improving mitochondrial function in neuronal cells and alleviating oxidative stress.