To study the mechanism of liraglutide improving cognitive impairment in alzheimer's disease rats by affecting nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 signaling pathway and ferroptosis activity in hippocampus
Objective To investigate the mechanism of liraglutide improving cognitive impairment in Alzheimer's disease(AD)rats by affecting nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)signaling pathway and ferroptosis activity in hippocampus.Methods Forty SD rats were randomly divided into control group,model group,liraglutide group and liraglutide+ferroptosis inducer erastin group,with 10 rats in each group.The AD model was established by intracerebroventricular injection of streptozotocin(STZ).The liraglutide group was intraperitoneally injected with liraglutide(200μg/kg)daily for 28 consecutive days.In the liraglutide+erastin group,intracerebroventricular injection of erastin(2.5 nmol/g)was performed simultaneously,followed by intraperitoneal injection of liraglutide(200 μg/kg)for 28 consecutive days.Morris water maze was used to detect cognitive function,ELISA was used to detect the levels of Aβ42 and glutathione(GSH)in the hippocampus,and Western blot was used to detect the expression levels of phosphorylated Tau protein,Nrf2 and GPX4 protein.Results The escape latency time of rats in control group,liraglutide group,liraglutide+erastin group and model group was successively prolonged on the 3rd,4th and 5th day,and the frequency of crossing the platform was successively reduced(P＜0.05).The level of A β42 and the expression levels of Nrf2,GPX4 and phosphorylated Tau protein in the hippocampus of control group,liraglutide group,liraglutide+erastin group and model group were increased in turn,the GSH level in hippocampus of control group,liraglutide+erastin group,liraglutide group and model group was decreased sequentially(P＜0.05).Conclusion Liraglutide may be involved in the improvement of cognitive impairment in AD rats by affecting Nrf2/GPX4 signaling pathway and ferroptosis activity in hippocampus.
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