| Senile plaques is one of the characteristic pathology changes in Alzheimer's disease(AD), its core composition isβ-amyloid protein(Aβ), which is formed byβ-secretase (BACE) andγ-secretase splitting amyloid precursor protein. BACE is an important rate-limiting enzyme in the process. Presenilin-1(PS-1) can promote the joint action of BACE andγ-secretase result in obvious increasing of AP production. PS-1 was regarded as the capital part ofγ-secretase compound. Thus, we may regulate the level of Aβby altering the expression of BACE and PS-1.Ginseng is a traditional Chinese medicine with the effect of intelligence promotion. Ginsenoside (GS) that is an active ingredient of ginseng can excite central nervous system. GSRb1 is diol form of ginsenoside. GSRb1 can nourish nerves, promote axon exogenesis, facilitate nerve regeneration and prolong survival time of hippocampal and cortical neuron. In recent years, the study has discovered that GSRb1 can inhibit tau protein over phosphorylation in hippocampal and cortical neuron and improve the learning dysmnesy in many experimental animals. However, the effect of GSRb1 on Aβproduction related protein expression in AD has not been reported. Therefore, the changes of Aβ, BACE and PS-1 expression in hippocampal formation of rats with AD were observed in the study for advance approaching pathogenesy of AD. Meanwhile, the effect of GSRb1 on them was compared. Materials and Methods1. Experimental animal grouping: 45 male Sprague-Dawley rats weighing 250g±20g were provided by Animal Experimental Center of China Medical University. The rats were randomized into control group, model group and treat group, with 15 in each. The rats in model group were treated with D-galactose intraperitoneal injection (60mg·kg-1·d-1) and aluminium trichloride intragastric administration (500mg·kg-1·d-1), lasting 4 weeks. GSRb1 (2.5mg·kg-1·d-1) was given to the rats in treat group after the establishment of AD model. The rats in control group were treated with same dose isotonic Na chloride.2. Morris water maze for testing learning and remembrance ability of rats was used. The average escape latency in every segment was recorded.3. Silver staining was done in order to assessment of AD model.4. Immunohistochemical staining for Aβ, BACE and PS-1 was performed.5. Western blotting for BACE and PS-1 were performed.6. Image collection analysis system was applied. The data were expressed as Mean±SD and were analyzed by SPSS 11.0 statistical package. The differences among group were compared with one-way analysis of variance. P<0.05 was regarded as the significant difference and P<0.01 was regarded as the extremely significant difference.Results1. Results of Morris water maze: All segmental escape latency in model group were prolonged compared with control group (P<0.05). The escape latency in treat group were shortened compared with model group (P<0.05).2. Results of silver staining: The nerve fibril derangement, twist, aggregation, and neurofibrillary tangles in cortical and hippocampal neuron of the rats in model group were seen. However, these changes were not seen in control group.3. Results of immunohistochemistry: The positive reaction product of AβBACE and PS-1 was stained yellow or buffy, most of them deposited in pyramidal cell layer of hippocampal CA1 and CA3 and granular cell layer of dentate gyrus. Compared with control group, the integrated optical density (IOD) of Aβ, BACE and PS-1 positive reaction product in model group was increased (P<0.01). The IOD of Aβ, BACE and PS-1 positive reaction product in treat group was decreased compared with model group (P<0.05).4. Results of western blotting: Compared with control group, the expression of BACE and PS-1 in hippocampal formation of the rats in model group was increased (P<0.01). The expression of BACE and PS-1 in hippocampal formation of the rats in treat group showed decrease tendency compared to model group (P<0.05).Conclusions1. The expression of Aβ, BACE and PS-1 in hippocampal formation of AD model rats shows up-regulation.2. The expression of Aβ, BACE and PS-1 in hippocampal formation of the rats in treat group was decreased compared with model group.3. The learning dysmnesy and pathology characteristic of AD could be simulated finely by D-galactose and aluminium trichloride. It may be a relatively ideal AD animal model.4. The learning and memory impairment of AD rats was improved by GSRb1. The mechanism was possibly due to down-regulation of BACE and PS-1 result in the decrease of Aβexpression in hippocampal formation after GSRb1 treatment.
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