Effect Of Estrogen Deprivation On The Formation Of Depression Induced By Cums In Mice And The Interventional Effect Of Yin Huo Tang On Experimental Postmenopausal Depression In Mice

Objective:The occurrence of menopausal depression is closely related to the decrease of estrogen level in postmenopausal women,but not all postmenopausal females suffer from depression,which suggests that the stimulation of environmental factors in addition to estrogen levels is also an important factor inducing depression in postmenopausal women.In this study,estrogen levels in animals were reduced by double puncture ovarian resection,in combination with chronic unpredictable mild stress(CUMS)stimulation,the effect of estrogen deficiency on depression was explored,and the intervention effect of Chinese herbal compound Yin Huo Tang(YHT)on menopausal depression mice was investigated through behavioral and biochemical methods.Methods:The first part of the experiment,the estrogen deprivation animal model was produced by bilateral ovarian resection in female mice,and chronic unpredictable mild stress(CUMS)stimulation was given to the mice to induce depression.Four methods of sucrose preference test(SPT),open field test(OFT),tail suspension test(TST)and forced swimming test(FST)were used to detect the depression behavior of animals,and the levels of cerebral 5-hydroxy tryptamine(5-HT)were measured by enzyme-linked immunosorbent assay(Elisa).In the second part of the experiment,the mice were randomly divided into 6 groups:sham operation group,model group,positive drug group,high dosage group of YHT,dosage group of YHT and low dosage group of YHT.In addition to the sham surgery group,the female mice were treated with bilateral ovarian resection and the model of menopausal depression mice was established by chronic unpredictable mild stress stimulation.After 4 weeks of drug therapy,the effects of drugs on the behavior of animal depression were detected by four methods,such as sucrose preference experiment,open field experiment,tail suspension test and forced swimming experiment,and the level of serotonin in brain were detected by enzyme-linked immunosorbent assay(ELISA).Results:The level of 5-hydroxy tryptamine(5-HT)decreased in the brain of mice combined with chronic unpredictable mild stimulation,behavioral changes(sugar preference decline is the loss of pleasure,autonomic activity reduction,the cumulative fixed time extension in both tail suspension test and forced swimming experiment),basically consistent with the clinical manifestations of menopausal depression.Simple ovarian removal does not appear depressive behavior in the short term,compared with simple CUMS stimulation,the recipient of ovarian removal combined with CUMS stimulation of mice appear depression-like behavior more earlier,suggesting that estrogen deficiency accelerated environmental factors induced depression formation.After the treatment of the YHT,the behavior of the depressive animals changed obviously(the preference of syrup increased,the autonomic activity increased,the cumulative fixed time in both the tail suspension experiment and the forced Swimming Experiment was shortened),while the level of 5-HT in the brain is increased.Conclusion:The results showed that the decrease of estrogen level in vivo led to the decrease of animal’s ability to resist external stress.Increase the susceptibility of depression;Chinese herbal compound Yin Huo Tang can significantly improve the typical symptoms of loss of pleasure and decrease of autonomic activity in female menopausal depression mice,and its mechanism is related to the regulation of 5-HT level in the brain.