Effect Of Heixiaoyaosan On Aβ Clearance In Hippocampus Of APP/PS1 Double Transgenic Mice

Objective To investigate the mechanism of improving the cognitive function of AD mice with HeiXiaoYao powder by observing the effect of HeiXiaoYao powder on behavioral,histopathological and Aβ clearance-related marker molecules in AD mice.Methods 42 SPF-level APP/PS1 transgenic mice aged 4 months and weighing 30±5g were used.10 mice of the same age group at the same age were used as blank groups.Forty-two transgenic mice were randomly divided into HeiXiaoYao powder high and low dose groups,positive drug control group,model group.After 3 months of intervention,Morris water maze ethology detected the learning and memory ability of each group of mice;Observating pathological on hippocampal tissue of AD mices by Hematoxylin-eosin staining.Immunohistochemical staining and Western blot were performed to detect the expression of Aβ1-42,GSK-3β,NEP and IDE protein in hippocampus of each group.Results (1)After 3 months of treatment,compared with the model group,the escape latency of the mice in each treatment group was shortened,and the number of crossing the original platform increased(P<0.05).Compared with the positive drug control group,the HeiXiaoYao powder high dose group had no significant difference in escape latency and the original platform(P>0.05),in which HeiXiaoYao powder high dose group and positive drug control group mice were superior to HeiXiaoYao powder low dose group(P<0.05).(2)Compared with the blank group,the degree of nerve cell damage in the hippocampus of the model group was severe.Compared with the model group,the degree of nerve cell damage in the hippocampus of each treatment group was reduced,and the HeiXiaoYao powder high dose group had a lighter injury than the positive drug control group.(3)Compared with the blank group,the expression of Aβ1-42 and GSK-3β were strongly positive expression in the model group,NEP and IDE was weakly positive in the model group(P<0.01).Compared with the model group,the expression of Aβ1-42 and GSK-3β weakened(P<0.01),and the expression of NEP and IDE increased in each treatment group(P<0.05).The HeiXiaoYao powder high dose group and the positive drug control group were superior to the HeiXiaoYao powder low dose group(P<0.05).There was no difference between the positive drug control group and the HeiXiaoYao powder low dose group(P>0.05).(4)Compared with the blank group,the relative expression levels of Aβ1-42 and GSK-3β protein in the model group increased significantly,and the relative expression levels of NEP and IDE proteins decreased significantly(P<0.05).Compared with the model group,the expression of Aβ1-42 and GSK-3β protein was significantly decreased in each treatment group,and the relative expression levels of NEP and IDE protein were significantly increased(P<0.05),And HeiXiaoYao powder high dose group is superior to HeiXiaoYao powder low dose group(P<0.05).Conclusion HeiXiaoYao powder can significantly improve the learning and memory ability of AD mice,which may be related to the regulation of abnormal deposition and degradation of Aβ in the hippocampus to reduce cognitive impairment in AD mice.