| Objective1.To explore the anti-hypoxia and anti-fatigue activities of Astragalus membranaceus aqueous extract.2.To explore the effect of plateau hypoxic environment on exercise capacity and the amelioration of Astragalus membranaceus aqueous extract.3.To explore the effect of plateau hypoxia environment on behavioral cognitive ability and the improvement effect of Astragalus membranaceus aqueous extract.Methods1.In normoxic sealed experiments,the anti-hypoxic activities of Astragalus membranaceus aqueous extract,Cistanche deserticola aqueous extract,Codonopsis pilosula aqueous extract and the mixture of aqueous extract of three herbs were compared by measuring the survival time of mice.The anti-fatigue activity of Astragalus membranaceus aqueous extract was investigated by exhaustive swimming test of rats.2.The rats were exposed to simulated hypobaric hypoxia experimental chamber(Altitude: 7500 m),combined with weight-bearing exhaustive swimming test.The exhaustive swimming time of rats was taken as the intuitive index and the related indexes such as energy storage substances,metabolites and oxidative stress products in serum,brain,liver and muscle of rats were detected to investigate the effect of plateau hypoxia on the exercise ability of rats and the improvement effect of Astragalus membranaceus aqueous extract on the exercise ability of rats at high altitude.3.The rats were exposed to simulated hypobaric hypoxia experimental chamber(Altitude: 7500 m).The behavioral cognitive ability of rats was tested by eight-arm maze.HE staining was used to observe the hippocampal morphology of rats,and the contents of MDA,GSH,ROS and T-SOD in hippocampus were measured.RT-PCR was used to determine the mRNA expression of mTOR,P70S6 K and 4E-BP1 in hippocampus,and the protein expression of p-mTOR,p-P70S6 K,p-4E-BP1 and Cleaved Caspase-3 were determined by Western Blot.Results1.Compared with Codonopsis pilosula,Cistanche deserticola and mixture group,the Astragalus membranaceus aqueous extractshowed better anti-hypoxia activity,and in the normoxic sealed experiment,the survival time of mice was significantly prolonged after the administration of the Astragalus membranaceus aqueous extract respectivelyin 0.5 g/kg and 1.0 g/kg doses.In the exhaustive swimming experiment,after the administration of Astragalus membranaceus aqueous extract in 0.35 g/kg dose,the exhaustive swimming time of rats was significantly prolonged,and the prolongation rate was 26.16%.2.Compared with the normoxia-exhausted swimming group,the swimming time of rats in hypoxia was significantly shortened(P<0.01),and the shortening rate was 41.37%.After theadministrationofAstragalus membranaceus aqueous extract,the swimming time ofrats was significantly prolonged in hypoxia experiment(P<0.01),with a prolongation rate of 32.03%.The tissue morphology of brain,liver and muscle were improved,and the energy storage substances in the body were increased.Besides,the accumulation of free radicals and metabolites were decreased,and the oxidative stress caused by hypoxia was alleviated to a certain extent.3.The behavioral cognitive ability of rats in the hypoxic control group was significantly reduced than that in the normoxic control group.After instragastric administration of Astragalus membranaceus aqueous extract,the behavioral cognitive ability of rats was significantly improved in the hypoxic condition,with the improvement of hippocampal CA1 area’s shapeand the alleviation of neuron damage.The contents of MDA and ROS in hippocampus were significantly decreased,while the content of GSH and activity of T-SOD in hippocampus were significantly increased.In additon,the mRNA expression of mTOR and P70S6 K and the protein expression of p-mTOR were significantly increased,while the mRNA expression of 4E-BP1 and the protein expression of p-4E-BP1 and Cleaved Caspase-3 were significantly decreased.ConclusionWhen exposed to plateau hypoxia environment,the exercise capacity and behavioral cognition of rats were significantly decreased,while the Astragalus membranaceus aqueous extract could obviously improve these abilities.The main mechanism was related to improving oxidative stress caused by hypoxia,reducing the accumulation of free radicals and metabolites,increasing the storage of energy-storing substances and antagonizing the inhibition of mTOR signal pathway under hypoxia. |