Influence Of Rapamycin On The Expression Of β-amyloid Protein In Model Mice With Alzheimer’s Disease

Object:. To observe the effect of Rapamycin on cognitive function in mice withAlzheimer’s disease and the expression of Aβ（beta-amyloid peptides） protein in the micebrain, and to explore its possible mechanism.Methods:503-month-old mice, half is male and half female.10wild type C57BL/6mice were normal control group, other40APP/PS1double transgenic AD mice wererandomly divided into two groups:10in AD model group and30in RAPA group. RAPAgroup was set according to different doses: low, medium and high groups,10mice in eachgroup. Low, medium and high dose RAPA groups were given a gavage of RAPA accordingto1.12mg kg-1d-1、2.24mg kg-1d-1、4.48mg kg-1d-1respectively, meanwhile normalcontrol group and AD model group were given a gavage of physiological saline of equalvolume, keeping for4weeks.24hours after the last administration, dowater maze and jump platform experiments respectively to detect the cognitive function ofthe mice. The expression of p-PKB （Protein kinase B with phosphorylation) ofhippocampal in mice, p70S6K（70kDa ribosomal protein S6kinase), Aβ1-42（beta-amyloidpeptides1-42）, mammalian target of rapamycin and p-mTOR(mammalian target ofrapamycin with phosphorylation) were detected by Western blot.Results: Compared with normal group, learning and memory performance in mice inAD model and RAPA groups decreased, expressions of Aβ1-42、mTOR、p-mTOR andp70S6K increased while expression of p-PKB decreased（P﹤0.05）；compared with ADmodel group, learning and memory performance in mice in RAPA group increased,expressions of Aβ1-42、mTOR、p-mTOR and p70S6K decreased while expression of p-PKBincreased（P﹤0.05）；comparisons among low、medium、high doses of RAPA groupsshowed that there were no statistical differences in learning and memory performance andexpressions of Aβ1-42，mTOR、p-mTOR、p70S6K and p-PKB.Conclusion: RAPA can relieve behavioral memory ability disorders in mice with AD,can reduce expressions of Aβ in the brain. The possible mechanism may be related toRAPA down-regulating the expression of mTOR, inhibitting the phosphorylation of mTOR, feedback-regulating the activity of PKB/mTOR signaling pathway and enhancing theexpression of p-PKB.