The Effect Of Shuyu Capsule And Main Consitution On ERK-CRED-BDNF Signal Pathway In Central Nervous System Of Depression Rat Model

Objective: To study the changes of ERK，CREB and BDNF levels in hippocampusand frontal of Liver-qi Depression Rat Model.To explore the microscopic centralmechanism of liver-qi depression, as well as the possible therapeutic mechanism oftraditional Chinese medicine Shuyu capsule and its component, from the aspect ofERK-CEB-BDNF signal pathway.Methods: We used the chronic mild stimulation (CMS) and binding method toprepare rat models suffering liver qi stagnation out of depression. Shuyu capsule,saikosaponin, paeoniflorin and fluoxetine are administrated to stressed rats.Western-blot was applied to detect the concentration of ERK,CREB and BDNF inhippocampus and frontal. RT-PCR method was applied to detect determine mRNAexpression of ERK,CREB and BDNF in hippocampus a,frontal.and the peripheral blood.ELISAwas used to detect the content of BDNF in Serum.Results:1.Compared with Control group, the weight of model group rat loses weightobviously（P<0.01） and the Sugar intake reduces remarkably（P<0.01）, Open field testscores were significantly reduced (P <0.01). Compared with model group, the weight of ratadministrated Shuyu capsule and fluoxetine are gained obviously（P<0.05）, Sugar intakewas significantly enhanced (P <0.01), open field test score was significantly increased (P<0.01);2.RT-PCR results: In hippocampus， Compared to Control group, Model group wassignificantly lower in ERK/CREB/BDNFmRNA expression (P<0.01). Compared to Modelgroup, Shuyu capsule and fluoxetine group was significantly higher in ERK/CREB/BDNFmRNA expression (P<0.01), The BDNFmRNA of saikosaponin groupwere significantly decreased (P<0.05).In frontal, Compared to Control group, Model group was significantly lower inERK/CREB/BDNFmRNA expression (P<0.01). Compared to Model group, Shuyu capsuleand fluoxetine group was significantly higher in ERK/CREB/BDNFmRNA expression(P<0.01). The CREBmRNA and BDNFmRNA were significantly decreased in aikosaponinand paeoniflorin group (P<0.05).3. Western blot results: In hippocampus， the ERK1/2,CREB and BDNF weresignificantly decreased in treated group compared to Con group(P <0.01). Compared tomodel group, treated group ERK1/2are significantly increased in hippocampus (P <0.01).The CREB of Shuyu capsule and fluoxetine group were significantly decreased (P<0.01).The CREB of saikosaponin group were significantly decreased (P<0.05).The BDNF weresignificantly decreased in treated group compared to Con group(P <0.01).In frontal, the ERK1/2,CREB and BDNF were significantly decreased in treatedgroup compared to Con group(P <0.01). Compared to model group, Shuyu capsule andfluoxetine group the ERK1/2,CREB and BDNF were significantly decreased(P <0.01).The CREB of saikosaponin group were significantly decreased (P<0.05). The BDNF ofsaikosaponin and paeoniflorin group were significantly decreased (P<0.05).4.ELISA results:The BDNF was significantly decreased in treated group compared to Congroup(P <0.01) in serum. Compared to Model group, treated groups BDNF aresignificantly increased in serum(P <0.01).Conclusion1.The pathogenesis of liver-qi depression associated with lower expression of ERK,CREBand BDNF in hippocampus and frontal.2. Shuyu capsule and main constitution alleviated the depressive-like behaviors andreversed the disruptions of the P-ERK, P-CREB and BDNF in stressed rats.3. The saikosaponin and paeoniflorin are main constitution of shuyu capsule withantidepressant effects, but can not reach the compound efficacy.