摘要

BACKGROUND: During onset and development of Alzheimer's disease, beta-amyloid (A beta) precursor protein (APP), beta-site amyloid precursor protein cleaving enzyme (BACE), and beta-amyloid are key genes and proteins in the A beta pathway, and over-expression of these genes can lead to A beta deposition in the brain. OBJECTIVE: To observe the influence of Longyanshen polysaccharides on expression of BACE, APP, and A beta 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 polysaccharides 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 intragastric administration, once per day, for 50 consecutive days. MAIN OUTCOME MEASURES: One hour after the final administration, immunohistochemical analysis was used to determine A beta expression in the cortex 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, A beta 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, A beta expression, as well as BACE and APP mRNA expression, were significantly decreased in the cerebral cortex 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 A beta in SAMP8 mice in a dose-dependent manner, and the effect was not worse than huperzine A.