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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.
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OBJECTIVE: To investigate the ameliorated effect and mechanisms of phenylethanoid glycosides from Pedicularis muscicola Maxim on high altitude memory impairment. METHODS: After successfully trained in the 8-arms radial maze, fifty Wistar rats were randomly divided into normoxic control group, hypoxia group, phenylethanoid glycosides 50, 200 and 400 mg · kg-1 groups (given corresponding dose). Normoxic control and hypoxia groups were administered with distilled water for a week. When drug delivery in the fourth day, hypoxia and phenylethanoid glycosides groups rats were exposed to a simulated of 7 500 m in a specially designed animal decompression chamber. Eight arms radial maze was used to measure spatial memory, HE stained was used to observe the cell morphology in brain tissue and biochemical technique was used to detect the content of MDA and ROS and enzymatic activity of GSH and SOD in brain tissue and serum. RESULTS: Compared with the normoxic control group, for hypoxia group rats, WME, RWE and TE were respectively increased by 800%, 71%, and 127.1% (P < 0.01) and neuron damage was significantly increased, the enzymatic activity of GSH and SOD were respectively decreased by 60.9% and 18.11% (P < 0.05, P < 0.01) in brain tissue and plasma while the content of MDA was increased in brain tissueby 74.8% (P < 0.01). Compared with the hypoxia group, for phenylethanoid glycosides 200, 400 mg · kg-1 groups rats, WME, RWE, TE were respectively decreased by 68.44%, 63.11%; 33.14%, 25.34% and 43.91%, 36.72% (P < 0.05, P < 0.01) and neuron damage was significantly decreased, the enzymatic activity of GSH were respectively increased by 219.76%, 180.75% and 32 81%, 24.10% (P < 0.05, P < 0.01) and the enzymatic activity of SOD were respectively increased by 9.57%, 13.88% and 15.41%, 15.45% (P < 0.05) in brain tissue and plasma, while the content of MDA in plasma were respectively decreased by 42.73%, 42.73% (P < 0.01) and MDA and ROS in brain tissue were respectively decreased by 61.71%, 42.79% and 40.76%, 23.53% (P < 0.01); for phenylethanoid glycosides 50 mg · kg-1 group rats, the corresponding indicators had been ameliorated, but there was no significant difference. CONCLUSION: Phenylethanoid glycosides of Pedicularis muscicola Maxim can ameliorate high altitude memory impairment, which its involved mechanism may be antioxidant stress and inhibition on cell damage.