Study On The Protective Effect And Mechanism Of Polygonatum Sibiricum Polysaccharide On Cognitive Impairment Caused By Chronic Stres

Objective:To study the preventive effect and the related mechanisms of Polysaccharide of Polygonati Rhizoma(PSP)on cognitive impairments induced by Chronic Stress in mice.Methods:The chronic stress experiment included two models: CSD and CRS,To evaluate the cognitive improvement effect of PSP on the animal behavior level,and to study the mechanism.The CSD and CRS were successively conducted.And 72 ICR mice with the body weight of 18-22 g were respectively purchased.They were randmly divided into the control group,the model group,the positive control(CSD:ginkgo biloba extract,CRS:Huperzine A)group,and the PSP(100,200,400 mg/kg)groups.The model was made after a room was adapted for a certain period of time.CSD model was carried out by a roller sleep disturbance instrument to turn 1 r/min at an interval of 1 min for mild awakening,lasting for 28 days;and CRS model was made by a chronic restraint instrument to bind the animals in the instrument from 22:00 to 8:00 every night to limit their movement for a total of 35 days.From the beginning,mice were given intragastric administration daily until sampling was completed,and the administration volume was0.1m L/10 g.After the completion of model building,the two batches of experiments were conducted with open field test,object recognition experiment,passive avoidance test and Morris water maze task.Finally,the mice were took blood from the orbit,centrifuged for the serum,and stripped for the hippocampus.In the mechanism tests,CSD model was used to detect the pro-inflammatory cytokine IL-1 in mouse serum and hippocampus β,Interleukin-6(IL-1 β,IL-6)level,the levels of neurotransmitters γ-Aminobutyric acid(GABA)and acetylcholine(Ach)in hippocampus.The levels of superoxide dismutase(SOD),malondialdehyde(MDA)and catalase(CAT)in serum and hippocampus,and the levels of corticosterone(CORT)and acetylcholine(Ach)in hippocampus were measured in CRS model mice.Results:The result of open field test showed that CSD and CRS did not affect the locomotor activities of the mice.Compared with the control group,the discrimination index(DI)of they model group in the object recognition experiment was significantly decreased,the errors times increased and the latent period decreased in the passive avoidance test,and a longer escape latency in MWM(Morris water maze)were observed in the model group.The results of mechanism detection showed,in CSD model,PSP could significantly reduce the levels of IL-6 and IL-1β in serum and hippocampus,and the content of GABA in hippocampus was significantly decreased,and Ach was significantly increased.In the CRS,PSP could significantly increased the SOD and CAT levels,significantly decreased MDA,the Ach were significantly increased and CORT decreased both in the serum and hippocampus.Conclusion:The results reveal that PSP treatment can effectively improve the cognitive impairments induced by CSD and CRS,and its cognition-improving effects might be related to regulate the levels of the oxidative stress and proinflammatory cytokines,regulation of HPA axis and neurotransmitter in the serum and hippocampus of mice.