| Objective:Depression has always been a psychiatric problem with a complex etiology facing the world,which has imposed a heavy medical and economic burden on many countries.According to statistics from the World Health Organization,nearly 800,000 people die from depression each year,and about 85% of depression patients are not treated.In recent years,the number of depression patients in China has increased significantly,and the treatment of depression needs to be resolved urgently.A large number of studies have shown that the gut microbiota affects the brain through the gut-brain axis,which is a new way to treat depression.In this study,Chronic Unpredictable Mild Stress(CUMS)was used to establish a mouse model of liver stagnation and spleen deficiency.The anti-depression mechanism of decoction provides a basis for the clinical application of Simotang.Methods:70 KM mice were randomly divided into control group,model group,fluoxetine group,mid-dose group of Simotang and high-dose group of Simotang after one week of acclimatization.Except for the control group,the remaining groups underwent CUMS modeling for 3 weeks.The modeling and gavage were performed simultaneously.The sucrose preference test,tail suspension experiment,forced swimming test and open field test were used to detect the behavioral changes of each group.At the end of modeling,the cerebral cortex of the mouse was taken,and the transcriptome and fecal metagenome were sequenced to select genes and gut microbiota with significant differences.Results:There was no difference in the sucrose preference test among the groups before modeling.After 3 weeks of modeling,the sucrose preference of the model group was significantly lower than that of the blank group,and the difference was significant(P<0.05).The dangling immobility time was significantly increased(P<0.05),swimming immobility time was significantly increased(P<0.05),and crossing the central grid was significantly reduced(P<0.01).Compared with the model group,there was no significant difference in sugar waterpreference between the Simotang group and the model group(P>0.05),the dangling immobility time was significantly reduced(P<0.05),the immobility time of forced swimming was not significantly different(P>0.05),and the crossing of the central grid was significant Increase(P<0.05).Based on transcriptome sequencing technology to study the effect of Simotang on gene expression in depression mice,through differentially expressed genes(DEG)analysis,it was found that in C_DNvsM_DN,128 and 133 differentially expressed genes were significantly upregulated and down-regulated;F_DNvsM_DN,Significantly up-regulated and down-regulateddifferentially expressed genes were 116 and 66 respectively;S-H_DNvsM_DN,significantly up-regulated and down-regulated differentially expressed genes were 100 and 147,respectively,most genes were related to depression,Alzheimer's disease,schizophrenia Syndrome,epilepsy and other mental diseases.Gene Ontology(GO)enrichment analysis found that there was significant enrichment in each pair of samples,mainly in the regulation of neuronal apoptosis,immune response,and glial cell development.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis found that the main pathways of the Simotang group include RAS,MAPK,PI3K-Akt,neurotrophic factors,RNA degradation,spliceosome,neuroactive receptor ligand interaction,and osteoclast Cell differentiation and peanut acid metabolism.Among them,MAPK,PI3K-Akt,neurotrophic factor,arachidonic acid metabolism are important pathways for depression.Based on metagenomic sequencing technology to study the effect of Simotang on the intestinal flora of depressive mice(Campylobacterales),Lachnospiraceae,Helicobacteraceae,Lactobacillus,and Bacteroides are significantly increased,and they have significant effects on ATP transport enzymes,transcriptional regulators,The abundance of lysine kinase has a significant increase,and the abundance of glycoside hydrolase significantly decreases.In the Simotang group,Firmicutes,Clostridiales,Campylobacterales,Lachnospiraceae,Helicobacteraceae,and Lactobacillus increased significantly High,Bacteroides significantly decreased,ATP transport enzymes,transcription regulators,histidine kinase abundance decreased significantly,glycoside hydrolase abundance increased significantly.Conclusion:The sucrose preference test,tail suspension test,forced swimming test,and open field test all have significant test results,indicating that the mice were successfully modeled.Based on the results,it can be seen that the three groups of experiments fluoxetine and Simotang all improved the depression-like behavior of mice,Suggesting that Simotang has obvious antidepressant effect.Simotang has obvious regulating effect on Bacteroides and Lactobacillus.Based on the results of transcriptome and metagenomic analysis,it is speculated that Simo Decoction regulates the abundance of Bacteroides and Lactobacillus through the intestinal brain axis to affect the activity of these pathways such as PI3K-Akt,MAPK,neurotrophins,and arachidonic acid metabolism. |
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