Key gene and protein changes in the beta-amyloid pathway following Longyanshen polysaccharides treatment in a mouse model of Alzheimer＇s disease

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),andβ-amyloid are key genes and proteins in the Aβpathway,and over-expression of these genes can lead to Aβdeposition in the brain. OBJECTIVE:To observe the influence of Longyanshen polysaccharides on expression of BACE, APP,and Aβin 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 Aβexpression 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,Aβexpression 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,Aβexpression,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 Aβin SAMP8 mice in a dose-dependent manner,and the effect was not worse than huperzine A.