基于Nrf2/ARE信号通路探讨中药山茱萸鞣质改善阿尔茨海默病小鼠认知障碍的作用机制OA

Objective To explore the protective effect and molecular mechanism of tannin in the traditional Chinese medicine Cornus officinalis tannin(SZYT)on cognitive impairment in mice with Alzheimer's disease(AD)induced by D-galactose(D-gal).Methods Sixty C57 mice were randomly divided into the blank control group,the D-gal model group,the positive control group(vitamin E 150 mg/kg),and the high,medium,and low(150,100,and 50 mg/kg)dose groups of SZYT,with 10 mice in each group.The AD mouse model was induced by intraperitoneal injection of D-gal,and the corre-sponding dose of the drug was administered by gavage intervention every day.The experimental period was maintained for 8 weeks.After the last gavage administration,the learning,memory and cognitive functions of mice were evaluated by Morris water maze and open field experiments.The activities of antioxidant enzymes such as superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),catalase(CAT)and the content of malondialdehyde(MDA)in hippocampal tissue were detected by spectrophotometry.The pathological changes in the hippocampus were observed by hematoxylin-eosin staining and Nissl staining.Western blot was used to investigate synaptic associated proteins microtubule-associated protein-2(MAP-2),postsynaptic density protein-95(PSD-95),synaptophysin(SYN),nuclear factor E2-related factor 2/antioxidant response element(Nrf2/ARE),antioxidant signaling pathway related proteins Nrf2,heme oxygenase-1(HO-1),and quinone oxidoreductase 1(NQO1).Results Compared with the D-gal model group,the escape latency of mice in the SZYT group in the Morris water maze test was significantly reduced,and the stay time in the target area and the number of times they crossed the platform were significantly increased(P＜0.01).In the open field experiment,the number of grid crossings,the duration of stay in the central area,the average speed and the total distance all increased significantly(P＜0.01).The biochemical results showed that compared with the D-gal model group,the activities of antioxidant enzymes such as SOD,GSH-Px and CAT in the brains of mice in the SZYT administration group significantly increased(P＜0.01),and the content of MDA significantly decreased(P＜0.01).The results of HE and Nissl staining indicated that compared with the D-gal model group,the neuronal damage in the SZYT administration group of mice was significantly alleviated.The Western blot results showed that,compared with the D-gal model group,the expression levels of proteins such as MAP-2,PSD-95,SYN,HO-1,NQO1,and Nrf2 in the brain of mice in the SZYT administration group were significantly increased(P＜0.01).Conclusion SZYT can improve cognitive impairment and neuronal synaptic injury in mice with AD induced by D-gal.The underlying molecular mechanism may be related to the upregulation of the Nrf2/ARE signaling pathway and the alleviation of oxidative stress in hippocampal tissue.