重复经颅磁联合高压氧通过调控AKT/GSK3β/β-catenin通路改善迟发性脑病神经功能OA

Objective:To investigate the effects of repetitive transcranial magnetic stimulation(rTMS)combined with hyperbaric oxygen(HBO)on neurological function in rats with delayed encephalopathy after a-cute carbon monoxide poisoning(DEACMP)and to explore the underlying mechanism based on the AKT/GSK3β/β-catenin signaling pathway.Methods:Wistar rats with qualified cognitive function,as screened by the Morris water maze test,were randomly divided into six groups(n=10 per group):Ctrl group,DEACMP model group,HBO group,rTMS group,rTMS+HBO combination group,and MK-2206 group(rTMS+HBO+AKT inhibitor MK-2206).The DEACMP model was established using a static carbon monoxide inhalation method.The Morris water maze test was employed to assess cognitive behavioral performance.Histological staining was used to observe pathological changes in hippocampal neurons.Serum levels of oxidative stress markers(ROS,MDA,SOD),inflammatory factors(IL-6,IL-18),and myelin basic protein(MBP)were measured by ELISA.Neuronal apoptosis was detected by TUNEL staining.The expression levels of apoptosis-related proteins(Bax,Bcl-2,CytC,Caspase-3)and key proteins in the AKT/GSK3β/β-catenin pathway(p-AKT/AKT,p-GSK3β Ser9/GSK3β Ser9,nuclear β-catenin)were determined by Western blotting.Re-sults:Compared with the Ctrl group,the escape latency,ROS and MDA levels,IL-6,IL-18 and MBP lev-els,neuronal apoptosis rate,Bax,CytC and Caspase-3 expression levels were significantly increased in the DEACMP group(P＜0.05).The number of crossing the platform,SOD level,Bcl-2,p-AKT/AKT,p-GSK3βSer9/GSK3βSer9 and nuclear β-catenin expression levels were significantly decreased(P＜0.05).Compared with DEACMP group,the escape latency,ROS and MDA levels,IL-6,IL-18 and MBP levels,neuronal apoptosis rate,Bax,CytC and Caspase-3 expression levels in HBO group and rTMS group were sig-nificantly decreased(P＜0.05).The number of crossing the platform,SOD level,Bcl-2,p-AKT/AKT,p-GSK3β Ser9/GSK3β Ser9 and nuclear β-catenin expression levels were significantly increased(P＜0.05).Compared with HBO group and rTMS group,the escape latency,ROS and MDA levels,IL-6,IL-18 and MBP levels,neuronal apoptosis rate,Bax,CytC and Caspase-3 expression levels in rTMS+HBO group were significantly decreased(P＜0.05).The number of crossing the platform,SOD level,Bcl-2,p-AKT/AKT,p-GSK3β Ser9/GSK3β Ser9 and nuclear β-catenin expression levels were significantly increased(P＜0.05).Compared with the rTMS+HBO group,the escape latency,ROS and MDA levels,IL-6,IL-18 and MBP lev-els,neuronal apoptosis rate,Bax,CytC and Caspase-3 expression levels were significantly increased in the MK-2206 group(P＜0.05).The number of crossing the platform,SOD level,Bcl-2,p-AKT/AKT,p-GSK3β Ser9/GSK3β Ser9 and nuclear β-caten in expression levels were significantly decreased(P＜0.05).Conclusion:The combination of rTMS and HBO exerts a significant neuroprotective effect against DEACMP.The mechanism is likely associated with the synergistic activation of the AKT/GSK3β/β-catenin signaling pathway,leading to the integrated suppression of oxidative stress,inflammatory response,and neuronal apop-tosis.