The Phenotype Of Learned Helplessness Model Balb/c Mice With Depression And Qi-deficiency Was Verified By Using The Intestinal Flora

Depression is a mental disorder with high recurrence rate and great harm.It is also an important contributor to the global disease burden.Although there are first-generation and second-generation antidepressants clinically,they are still ineffective in some patients due to obvious adverse reactions and poor lasting efficacy.Therefore,looking for traditional Chinese medicine with small side effects and lasting curative effect is an important source of antidepressants.Traditional Chinese medicine advocates individualized medication,distinguishes between the manifestations of depression and syndromes,and selects the appropriate treatment prescription,which has a good curative effect in the clinical treatment of depression.We found that Balb/c mice can produce qi-deficiency depression under stress.This study mainly observed the antidepressant effect of zengyi decoction and liqi decoction blueberry pill on chronic learning helplessness stress mice,the improvement effect of qi-deficiency depression and the persistence of drug effect on this strain mice after treatment,and explored whether the drug could improve the symptoms of depression and qi-deficiency in mice by improving intestinal flora.Objective:1.After chronic learned helplessness modeling,Balb/c mice showed symptoms of qi-asthenia depression,and prescriptions were used to counter the symptoms of qi-asthenia depression.2.Through the perspective of intestinal flora,the efficacy and persistence of Guipi decoction in the treatment of depression and qi-deficiency in Balb/c strain mice were studied,and its functional flora was discovered.Methods:Balb/c strain male mice were given learned helplessness(LH)to induce the establishment of depression disease model,and the model was constructed for 13 days.By Learned helplessness testing(LH),Tail suspension test(TST),Forced swimming test(FST)and Novelty suppressed bean test(NSF)to judge the depression disease,by Grip strength test,Loaded swim test,Degree of redness test to judge the debility.LH group were randomly divided into Veh group,Yueju(YJ),Guipi Decoction(GDP)group and the Fluoxetine group(FLX).The CTL and Veh groups were given 0.9%normal saline by gavage,the YJ group was given 0.2g/ml YJ pills by gavage,the GPD group was given Guipi decoction by gavage,and the FLX group was given 2mg/ml fluoxetine by intraperitoneal injection.A series of behavioral tests were performed one week after administration and again four days after discontinuation.The efficacy of the drugs was evaluated by evaluating their antidepressant effect and improvement effect on qi-deficiency syndrome.After the end of the behavioral test,the feces of the above five groups were taken and analyzed by 16sRNA sequencing.Results:1.Balb/c mice developed depression-like behavior after LH stress:immobility time significantly increased.After given stress,Balb/c model mice developed qi-deficiency symptoms such as reduced loaded swim time,decreased grip strength power,and decreased degree of redness.After 7 days of continuous administration,the performance of immobility time increased and avoidance failure frequency decreased in the groups of YJ,GPD group and Fix group,which proved to have an antidepressant effect on Balb/c mice.However,the improvement of qi-deficiency behaviors such as loaded swim,grip strength and degree of redness in the mice with Guipi decoction was significantly better than that of YJ and Fix.2.According to the behavioral test results on the fourth day after drug withdrawal,Fix and YJ had little effect on the symptoms of depression and qi-deficiency in mice,but Guipi decoction could still improve the symptoms of depression and qi-deficiency in mice,proving that the efficacy of Guipi decoction was more sustainable.Guipi decoction can improve its syndrome phenotype and its effect is relatively lasting,which may be affected by intestinal flora.3.GPD not only improved the diversity and structure of intestinal microbiota of LH mice,but also played a.role in the relative abundance of.intestinal microbiota.The intestinal microbiota of the model group was significantly different from that of the CTL group,the GPD group and the Flx group.Compared with the CLT group,the relative abundance of bacteroidetes decreased and the relative abundance of firmicutes increased in the model group.Compared with the model group,the relative abundance of bacteroidetes increased in the YJ and the GPD.Guipi decoction significantly changed the abundance of bacteroidetes in the cecum contents of LH mice.Compared with the CTL group,the relative abundance of bacteroidetes decreased and the relative abundance of firmicutes increased in the Veh group.Compared with the Veh group,the relative abundance of bacteroidetes increased in the YJ group and the GPD group.It was proved that Guipi decoction could improve the symptoms of depression and qi-deficiency in mice by improving the bacteroidetes in the intestinal flora of mice.Compared with western medicine fluoxetine and Chinese medicine YJ pills,Guipi decoction has more lasting effect.Conclusion:1.After LH stress,Balb/c mice showed qi-deficiency-like depression.Guipi decoction can improve its syndrome phenotype and its effect is relatively lasting,which may be affected by intestinal flora.2.Compared with western medicine Flx and Chinese medicine YJ pills,Guipi decoction has a more lasting effect.