摘要BACKGROUND:During onset and development of Alzheimer's disease,β-amyloid (Aβ) precursor protein (APP),β-site amyloid precursor protein cleaving enzyme (BACE),and β-amyloid are key genes and proteins in the Aβ pathway,and over-expression of these genes can lead to Aβ deposition in the brain.OBJECTIVE:To observe the influence of Longyanshen polysaccharides on expression of BACE,APP,and Aβ in the senescence-accelerated mouse prone/8 (SAMP8) brain,and to compare these effects with huperzine A treatment.DESIGN,TIME AND SETTING:A randomized,controlled,neurobiochemical experiment was performed at the Department of Pharmacology and Scientific Experimental Center of Guangxi Medical University from September 2005 to January 2008.MATERIALS:Longyanshen polysacchaddes powder was extracted from the dried slices of the medicinal plant Longyanshen.The active component,Longyanshen polysaccharides,was provided by the Department of Pharmacology,Guangxi Medical University;huperzine A was purchased from Yuzhong Drug Manufactory,China.METHODS:Healthy SAMP8 mice were used to establish a model of Alzheimer's disease.A total of 50 SAMP8 mice were randomly assigned to 5 groups (n=10):SAMP8,huperzine A,low-,middle-,and high-dose polysaccharides.In addition,10 senescence-accelerated mouse resistant 1 (SAMR1) mice were selected as normal controls.SAMP8 and SAMR1 mice were administered 30 mL/kg normal saline;the huperzine A group was administered 0.02 mg/kg huperzine A;the low-,middle-,and high-dose polysaccharides groups were respectively administered 45,90,and 180 mg/kg Longyanshen polysaccharides.Each group was treated by intragastdc administration,once per day,for 50 consecutive days.MAIN OUTCOME MEASURES:One hour after the final administration,immunohistochemical analysis was used to determine Aβ expression in the codex and hippocampus of SAMP8 mice.Reverse-transcription polymerase chain reaction was used to determine mRNA levels of BACE and APP in SAMP8 brain tissue.RESULTS:Compared with the SAMR1 group,Aβ expression in the cerebral cortex and hippocampus,as well as expression of BACE,APP mRNA in the brain was significantly increased in the SAMP8 group (P＜0.05-0.01).Compared with the SAMP8 group,Aβ expression,as well as BACE and APP mRNA expression,were significantly decreased in the cerebral codex and hippocampus of huperzine A and low-,middle-,and high-dose polysaccharides groups (P＜0.05-0.01).In particular,the effect of high-dose polysaccharides was the most significant (P＜0.05-0.01).CONCLUSION:Longyanshen polysaccharides reduced or inhibited over-expression of BACE,APP,and Aβ in SAMP8 mice in a dose-dependent manner,and the effect was not worse than huperzine A.