| Objective:Postpartum depression(PPD)is a mood disorder with a high prevalence.The pathomechanism of PPD is complex and remains unclear,though the nervous,endocrine,and immune systems in combination appear to be involved.Shen-Qi-Jie-Yu-Fang(SJ Fang)is composed of eight Chinese medicinal herbs.It is widely used in traditional Chinese medicine for treating postpartum depression(PPD).Previous studies have shown that SJF treats PPD through the neuroendocrine mechanism.PPD is closely linked to the immune system through activa-tion of the inflammatory response.Activation of the T-cell system has been shown to be involved in susceptibility to mood disorder.The aim of this study is to further investigate the effect of SJ Fang on the immune system,including the inflammatory response system and CD4+CD25+regulatory T(Treg)cells.Methods:Total 90 Sprague Dawley rats were used to create an animal model of PPD by inducing hormone-simulated pregnancy(HSP model)followed by hormone withdrawal.Basing on the similar open field test(OFT)scores,the rats were randomly divided into five groups:normal group,sham-operated group,HSP group,SJ Fang group and fluoxetine group.Total 72 Pregnant Sprague Dawley rats were used to create an animal model of PPD(MS model)by separatinging mother rats from pups for 4 hours per day lasting 21days.Basing on the similar open field test(OFT)scores,the rats were randomly divided into four groups:normal group,MS group,SJ Fang group and fluoxetine group.The PPD rats were treated with SJF or fluoxetine for 1,2,and 4 weeks.Depressive behavior in the rats was evaluated by the forced swim test,sucrose consumption test,and open field test.Serum interleukin(IL)-1?and IL-6 were evaluated by enzyme-linked immunosorbent assay,and gene and protein expressions of IL-1RI,IL-6R,and gp130 in the hippocampus were observed by RT-qPCR and Western blot.Levels of Treg cells and Th 17 in peripheral blood were measured by flow cytometry analysis.Results:Study 1:HSP model rats were generally in poor condition,with sparse,dim and straggly hair,and their exploration and modification activities reduced.They had decreased weight,decreased horizontal and vertical movements in the OFT,decreased sucrose intake and increased immobility time in the FST at 1,2 and 4 weeks.SJ Fang and fluoxetine can improve those behavioral performances of PPD rats at 1,2 and 4 weeks.MS model rats were generally in poor condition,with sparse,dim and straggly hair,and their exploration and modification activities reduced with loose musles and stools.MS model rats had decreased weight(P<0.05),decreased horizontal and vertical movements in the OFT(P<0.01)from 1 week to 4 weeks.Immobility time in the FST of MS model rats increased and sucrose intake and strugle time in FST decreased at 1 and 2 weeks(P<0.05),and these indicators became recovered at 4 weeks.SJ Fang and fluoxetine can improve those behavioral performances of PPD rats at 1,2 and 4 weeks.Study 2:Serum IL-1? in HSP model rats increased at 1 week(P<0.05)and declined from then on to lower than normal at 4 weeks(P<0.05),while serum IL-6 increased at 1,2,and 4 weeks(P<0.05).Both IL-1? and IL-6 levels were downregulated by SJF and fluoxetine.Changes in gene and protein expressions of IL-1RI and gp130 in HSP model rats were consistent with changes in serum IL-l?(P<0.05),and were able to be regulated by SJ Fang and fluoxetine.Gene and protein expressions of IL-6R showed no difference from normal rats at 1,2 and 4 weeks.MS model rats' IL-1? level increased at 1 week(P<0.05)and declined from then on to lower than normal at 4 weeks(P<0.05),which was similar to HSP model rats.Serum IL-6 increased at 1 and 2 weeks(P<0.05),but showed no difference from normal rats at 4 weeks.Gene and protein expressions of IL-1RI and gp130 increased at 1 and 2 weeks and decreased at 4 weeks,which similar to HSP model rats.Gene and protein expressions of IL-6R decreased at lweek.SJ Fang and fluoxetine can regulated these indicators at 1,2 and 4 weeks.Study 3:In HSP model rats,the levels of Treg cells decreased at 1 and 2 weeks then recoveried to normal at 4 weeks,and SJ Fang and fluoxetine can increase Treg cells at 2 and 4 weeks.Th17 cells in HSP model rats decreased at 1 and 2 weeks and then increased more than normal at 4 weeks,which could be up regulated by SJ Fang and fluoxetine at 1 and 2 weeks.The ratio of Treg/Th 17 in HSP model rats increased at 1 and 2 weeks and then decreased to levels less than normal at 4 weeks,which could be down regulated by SJ Fang and fluoxetine at 1 and 2 weeks.In MS model rats the levels of Treg cells decreased at 1 week,increased at 2 weeks and then recoveried to normal level at 4 weeks(P<0.05).SJ Fang and fluoxetine can increase Treg cells at 1 week and at 2 weeks the Treg cells in SJ Fang group had no difference with normal group;Th17 cells increased at 1 week(P<0.05)and declined from then on to lower than normal at 4 weeks(P<0.05),which was similar to IL-1? both in two models.SJ Fang and fluoxetine can decrease Th17 cells at 1 and 2 weeks;The ratio of Treg/Th17 in MS model rats decreased at 1 and 2 weeks and then increased at 4 weeks,which could be up regulated by SJ Fang and fluoxetine.Conclusion:1.Both two PPD models could minic the behavioral performances of human PPD including hopeless,decreased interesting,blue mood,and low activity.SJF and fluoxetine could improve these behavioral performancess.2.There exists an imbalance between inflammation and inflammation inhibition with the overreaction of inflammation in PPD.SJF and fluoxetine can attenuate dysfunction of proinflammatory cytokines by interfering with their receptors at different phases of PPD.There exists an imbalance between Treg/Th17 cells in PPD.And SJF and fluoxetine can increase Treg cells and decreased Th17 cells to suppress inflammation.3.Dysfunction of proinflammatory cytokines in different stages of PPD was attenuated by SJF and fluoxetine through the modulation of serum concentrations of IL-1? and IL-6,expressions of IL-1RI,and gp130 in the hippocampus,and Treg cells and Th17 cells in peripheral blood. |
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