Phenylethanoid glycosides of Pedicularis muscicola ameliorate high altitude-induced memory impairment by activating mTOR signal pathway / 药学实践杂志

ABSTRACT

Objective To investigate the mechanism of phenylethanoid glycosides of pedicularis muscicola Maxim ameliorating high altitude memory impairmentby activating mTOR signal pathway.Methods 60 clean male Wistar rats were randomly divided into normoxic control group, hypoxia group, PhGs low, medium and high dose groups(50, 200, 400 mg/kg by oral administration).Normoxic control and hypoxia groups were administered with sterile injection water for 7 days.On the fourth day of drug treatment, hypoxia and PhGs groups were exposed to a specially designed animal decompression chamber, which simulated 7 500 m high altitude environment.The expression levels of mTOR, P70S6K and 4E-BP1 mRNA in hippocampus were detected by SYBR Green real-time PCR.The expression levels of p-mTOR, p-P70S6k and p-4E-BP1 protein in hippocampus were detected by Western blot.Results For hypoxia group rats, mTORand P70S6k mRNA repression, p-mTOR and p-P70S6K protein repression were respectively decreased by 22.50%, 26.00%, 42.28% and 11.70%(P<0.05, P<0.01), 4E-BP1 mRNA repression and p-4E-BP1 protein repression were respectively increased by 41.28%, 111.86%(P<0.01) in comparison tonormoxic control group.Compared with hypoxia group,for PhGs low dose group rats, 4E-BP1 mRNA repression and p-4E-BP1 protein repression were respectively decreased by 77.33% and 82.4%(P<0.01), p-P70S6K protein repression was increased by 32.53%(P<0.01).For PhGs medium, high dose groups, mTOR and P70S6k mRNA repression,p-mTOR and p-P70S6K protein repression were respectively increased by 64.56%, 60.76%;14.86%, 20.27%;65.12%, 94.17% and 56.63%, 78.31%(P<0.01), 4E-BP1 mRNA repression and p-4E-BP1 protein repression were respectively decreased by 72.67%, 71.57% and 57.6%, 40%(P<0.01).Conclusion Phenylethanoid glycosides of Pedicularis muscicola Maxim can ameliorate high altitude-induced memory impairment.This protective mechanism may due to the activation of mTOR signal pathway.