Objective To investigate the synergistic effect of extract of Ginkgo biloba leaves(EGb 761)combined with donepezil on the Alzheimer's disease(AD)model rats and its mechanism.Methods A total of 72 male SD rats were selected and randomly divided into the normal group(equal volume of normal saline),the sham operation group(equal volume of normal saline),the model group(equal volume of normal saline),the donepezil group(25 mg/kg),the EGb 761 group(50 mg/kg),and the combination group(25 mg/kg donepezil+50 mg/kg EGb 761),with 12 rats in each group.After intraperitoneal injection of 300 mg/kg chloral hydrate for anesthesia,the rats' bilateral hippocampi were injected into the aggregated Aβ 25-35(10 µL)at a rate of 1 µL/min to replicate the AD rat models.After successful modeling,the rats in each group were given corresponding drug or normal saline by gavage once a day for two treatment courses(10 d for each course,with an interval of 3 d).The Morris water maze test was used to assess the cognitive and memory abilities of rats.The TUNEL staining method was used to observe the apoptosis of hippocampal neurons in rats,and the apoptotic index was calculated.The enzyme-linked immunosorbent assay(ELISA)was used to detect the serum acetylcholinesterase(AChE),malondialdehyde(MDA)and superoxide dismutase(SOD)levels in rats.The Western blot was used to detect the expression levels of nuclear factor(NF)-κB pathway-related proteins including p-IKKα,p-IκBα and p-NF-κB in hippocampal tissue of rats.Results Compared with those in the model group,the escape latency in each drug group significantly shortened on the 6th day of Morris water maze test,the frequency of crossing the platform and time-consuming percentage in quadrant Ⅰ significantly increased on the 7th day;the positive cell count and the apoptotic index of hippocampal neurons in each drug group significantly decreased(P<0.05);the AChE and MDA levels in each drug group significantly decreased,while the SOD level significantly increased(P<0.05);the expression levels of NF-κB pathway-related proteins including p-IKKα,p-IκBα and p-NF-κB in each drug group significantly increased(P<0.05).The above indexes in the combination group were significantly better(P<0.05).Conclusion EGb 761 combined with donepezil can synergistically improve the memory ability of AD model rats,and its mechanism may be related to the decreased apoptosis after activation of the NF-κB pathway in hippocampal neurons.
关键词
银杏叶提取物/多奈哌齐/EGb/761/阿尔茨海默病/核因子-κB通路/认知功能/细胞凋亡
Key words
extract of Ginkgo biloba leaves/donepezil/EGb 761/Alzheimer's disease/nuclear factor-κB pathway/cognitive function/apoptosis
维普
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