To Study The Effect Of Paeoniflorin On The ERK/CREB Signaling Pathway Of Model Hippocampal And Its Mechanism

ObjectiveTo investigate the effect of paeoniflorin on ethology and pathological structure of hippocampus of CUMS rats;to investigate the effect of paeoniflorin on gene expression of ERK1/2 and CREB in CUMS rat hippocampus;to investigate the effect of paeoniflorin on ERK1/2,p-ERK1/2,CREB、p-CREB protein expression in hippocampus of CUMS rats;to study the effect of paeoniflorin on the ERK/CREB signaling pathway of model hippocampal and its mechanismMethod(1)Effect of paeoniflorin on ethology and pathological structure of hippocampus of CUMS ratsThe male SD rats were randomly divided into control group,model group,paeoniflorin 30mg/kg group,paeoniflorin 30mg/kg+U0126 group,paeoniflorin 60mg/kg group,paeoniflorin 60mg/kg+U0126 group,U0126 group.Weight change experiments,sucrose consumption test,open field test,forced swimming test and HE staining,Nissl staining was made to investigate the effect of paeoniflorin on ethology and pathological structure of hippocampus of CUMS rats.(2)Effect of paeoniflorin on ERK1/2、CREB gene expression in hippocampus of CUMS ratsBy copying CUMS rats,RT-PCR was used to investigate the influence of paeoniflorin on gene expression of ERK1/2 and CREB in.CUMS rat hippocampus to detectthe influence of paeoniflorin on gene expression of ERK1/2 and CREB in.CUMS rat hippocampus.Effect of paeoniflorin on protein expression of ERK1/2、p-ERK 1/2、CREB、p-CREB in hippocampus of CUMS rats(3)Effect of paeoniflorin on protein expression of ERK 1/2、p-ERK 1/2、CREB、p-CREB in hippocampus of CUMS ratsBy copying CUMS rat model,using Western-Blotting assay the protein expression of ERK、p-ERK、CREB、p-CREB in hippocampus of CUMS rats,study protein expression in hippocampus of CUMS rats.Result(1)Behavioral experiments showed that:Compared with the control group,body weight,sugar preference index,locomotor activity reduced in the model group rats,swimming immobility time increases,there are significant differences(P<0.05,P<0.01);Compared with the model group,body weight,sugar preference index,increased locomotor activity in the group of paeoniflorin 30,60mg/kg,swimming immobility time decreased,there are significant differences(P<0.05,P<0.01),U0126 was no significant difference compared with the model group,but its body weight,sugar preference index,locomotor activity reduced,swimming immobility time increases with the model group,showed similar depression-like behavior.Compared with the group of paeoniflorin 30,60mg/kg,the group of paeoniflorin 30mg/kg+U0126,60mg/kg+U0126 of rats reduced in body weight,sugar preference index,locomotor activity,increased swimming immobility time,showed significant difference(P<0.05,P<0.01).Pathological histology experimental results show:the model group compared with blank group visible hippocampal nerve cells arranged disorder loose,austenite shallow dye and partly dissolved;the U0126 group compared with model group showed rats hippocampal nerve nucleus pycnosis,loosely arranged,austenite shallow dye,disordered arrangement,the degree of cell damage was similar to model group.The group of 30,60mg/kg group compared with model group showed hippocampal nerve cells arranged a mild disorder,part of the nucleus pycnosis,austenite shallow dye,showed cell damage change reduced in the model group;Compared with the group of Paeoniflorin 30,60mg/kg,the group of Paeoniflorin 30mg/kg+U0126,60mg/kg+U0126 aggravated cell damage.(2)RT-PCR results showed that:compared with the control group,the expression of ERK1 mRNA,ERK2 mRNA,CREB mRNA in model hippocampal was significantly decreased(P<0.05,P<0.0 1);Compared with the model group,the expression of ERK1 mRNA,ERK2 mRNA,CREB mRNA in the group of Paeoniflorin 30,60mg/kg was significantly increased(P<0.05,P<0.01);(3)Western-Blotting Results:Compared with the control group,the protein expression.of ERK,p-ERK,CREB,p-CREB was significantly decreased in model group(P<0.05,P<0.01);Compared with the model group,the protein expression.of ERK,p-ERK,CREB,p-CREB was significantly increased in paeoniflorin 30,60mg/kg group(P<0.05,P<0.01),U0126 hippocampal p-ERK,p-CREB protein expression was significantly decreased(P<0.01).Compared with paeoniflorin group 30,60mg/kg,the expression of p-ERK was significantly decreased in paeoniflorin 30mg/kg+U0126,60mg/kg+U0126 group(P<0.05,P<0.01).Conclusion(1)Paeoniflorin can significantly increase the CUMS rats weight changes,the sugar water preference index,independent activity,reduce the swimming time,can obviously relieve CUMS rats in depression behavior,improve the pathological injury of hippocampal neurons;U0126 inhibitors can adersely affect paeoniflorin ease CUMS rats behavior and the effect of the protection of nerve cells in the hippocampus.(2)Paeoniflorin can significantly increase the expression of ERK1 mRNA,ERK2 mRNA,CREB mRNA in CUMS rat hippocampus,suggesting paeoniflorin possible by increasing the expression of ERK1 mRNA,ERK2 mRNA,CREB mRNA expression in ERK/CREB signaling pathway,and thus play a role in antidepressant.(3)Paeoniflorin could significantly increase the expression of ERK,p-ERK,CREB,p-CREB protein in hippocampal,U0126 inhibitor antagonizing paeoniflorin by upregulating the expression of ERK-CREB pathway plays a role in depression,suggesting possible paeoniflorin by adjusting the ERK/CREB protein expression signal transduction pathways involved in antidepressant effects.