| With the rapid development of society,people are getting more and more stressed in their daily work and life.Sleep problems have gradually become one of the main problems affecting people’s daily lives.Sleep deprivation refer to the inability ensure adequate and continuous sleep due to environmental or self-factor,causing mental burnout,inability to concentrate,decreased ability to learn and memory and other problems.The adverse effects of sleep deprivation on the body have become one of the problems that have long troubled people.The vine tea is the stems and leaves of Ampelopsis grossedentata(Hand.-Mazz.)W.T.Wang,which has the effects of clearing away heat and dampness,calming liver and lowering blood pressure,and promoting blood circulation.Modern pharmacological studies have shown that Ampelopsis grossedentata has a variety of pharmacological activities,such as anti-cancer,anti-inflammatory,antibacterial,anti-oxidation,hypolipidemic,liver protection and so on.In recent years,the protective effect of Ampelopsis grossedentata on the nervous system has received extensive attention.The previous research group showed that acute sleep deprivation could cause memory impairment in mice,and Dihydromyricetin could improve nerve damage caused by sleep deprivation by reducing oxidative stress in the brain,inhibiting inflammatory factors and apoptosis.Therefore,based on research evidence in the past,we study the effect and mechanism of Ampelopsis grossedentata on learning and memory in chronic sleep deprived mice,and lay a scientific foundation for the development and utilization of Ampelopsis grossedentata to improve the cognitive impairment of sleep deprivation.Object:(1)To explore the effect and mechanism of Ampelopsis grossedentata and its main ingredients dihydromyricetin on learning and memory impairment induced by chronic sleep deprivation.(2)To explore the protective mechanism of Ampelopsis grossedentata on the nervous system.(3)To explore the regulation effect of Ampelopsis grossedentata and dihydromyricetin on gut microbiota of mice with chronic sleep deprivation based on metagenomic sequencing technology.Method:(1)ICR mice were used as experimental animals,and were separate into normal group,model group,dihydromyricetin high and low dose groups,Ampelopsis grossedentata high and low dose groups a modified multi-platform method(MMPM)was used to establish a model chronic sleep deprivation.The normal autonomic activity of mice was evaluated by open field test,and the spatial learning and memory abilities evaluated by new object recognition experiment,Morris water maze and passive avoidance test.Elisa method was used to detect the levels of inflammatory factors in the hippocampus and cortex of mice.Nissl staining and immunohistochemistry were used to evaluate the morphological changes of nerve cells and glial cells.Quantitative Real-time PCR(QPCR)was used to detect the related gene expression on TLR4/MyD88/NF-κB pathway.(2)Based on TCMSP database,PubChem database,Metascape and other online analysis systems,the effective compounds of Ampelopsis grossedentata and neuropsychiatric diseases and targets were screened,and the "compound-target" and"target-disease" network diagrams were made.The String database was used to map protein interaction(PPI)networks and find key targets.(3)The α diversity,changed structure and relative abundance of gut microbiota in mice after chronic sleep deprivation were analyzed based on metagenomic sequencing technology.Results:(1)After 21 days of sleep deprivation and administration,the autonomous activity and space exploration ability of mice were not affected.Compared with the control group,identification index of the model group in the new object recognition test was significantly reduced.In the Morris water maze test,the escape latency of the model group mice to find the platform increased significantly,and the time and number of crossing the target quadrant and the number of crossing the platform during the test phase significantly reduced;After the administration of Ampelopsis grossedentata and Dihydromyricetin,the mice’s spatial learning and memory ability in the new objects test and Morris water maze test were significantly improved.(2)The flavonoids,phenols,volatile oils,and steroids in vine tea work together to exert neuroprotective effects,and flavonoids are the main ingredients for neuroprotection.GO and KEGG analysis were mainly related to synaptic signaling,protein kinase activity,and response to reactive oxygen species,cancer pathways,neuroactive ligand-receptor interaction pathways,inflammation pathways,oxidative stress-related pathways.PPI network found that APP,TP53,HSP90AA1,MAPK1,AKT1 and other 5 targets may be the key targets to exert its neuroprotective effect.(3)Chronic sleep deprivation didn’t affect the a diversity of intestinal flora in mice,but regulated the structure of intestinal flora and the taxa levels of mice.Ampelopsis grossedentata and dihydromyricetin could regulate the abundance of specific groups of gut microbiota in mice with chronic sleep deprivation,especially Lactobacillus and Eubacterium.Conclusion:Ampelopsis grossedentata and dihydromyricetin can improve the memory impairment by reducing the neuroinflammation of mice induced by chronic sleep deprivation.The mechanism may be related to the TLR4/MyD88/NF-κB pathway.The network pharmacology results show that the function of vine tea was multiple-component and multiple-target.The mechanism of vine tea’s neuroprotective effect involved regulating protein kinase activity,decreasing oxidative stress,and ameliorating neuroinflammation.It might have a potential effect on Alzheimer’s disease,depression and bipolar disorder.Chronic sleep deprivation can cause gut microbiota disorders of mice,and Ampelopsis grossedentata and dihydromyricetin may affect the central nervous system and inflammation by regulating specific microbiota groups in the intestine,thereby improving learning and memory disorders caused by chronic sleep deprivation. |
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