| Objective: In this subject,we adopted depression model animals,to abserve whether Shuyu Prescription could improved the depression symptom of them by means of regulating and controlling neuroplasticity in brain with improving RAS-MAPK-ERK Signal conduction pathway,and to expound its mechanism of action,in order to provide effective and reliable theoretical basis and experimental data to apply Shuyu Prescription on clinical.Methods:Experiment one: We adopted solitary approach combined with Chronic unpredictable stress to establish depression rat model,and by the way of open field test and sucrose preference test to abserve the effect on behavioristics of depression model rats with Shuyu Prescription;and by the way of ELISA to abserve the effect on neurotrophy,neuroprotection and neuroplasticity in brain of depression model rats with Shuyu Prescription with detection the activity of related neurotrophic factor(included NGF,BDNF,CREB)in cerebral cortex of rats in every group;and by the way of immunohistochemical and Western Blot to detect the expression of Ras,MAPK,ERK in hippocampus of rats in every group,and by the way of real-time PCR to detect the expression of RASmRNA ? MAPKmRNA ? ERKmRNA in hippocampus of rats in every group,in order to abserve the effect on regulating and controlling of RAS-MAPK-ERK Signal conduction pathway in hippocampus of depression model rats with Shuyu Prescription,and to probe its molecule mechanism of regulation on neuroplasticityExperiment second: We adopted the way of Chronic oral glucocorticoid to establish depression mouse model,and by the way of open field test,elevated plus maze experiment and forced swimming test to abserve the effect on behavioristics of depression model mouses with Shuyu Prescription;and by the way of ELISA to abserve the effect on neurotrophy,neuroprotection and neuroplasticity in brain ofdepression model mouses with Shuyu Prescription with detection the activity of related neurotrophic factor(included NGF,BDNF,CREB)in cerebral cortex of mouses in every group;and by the way of immunohistochemical and Western Blot to detect the expression of RAS,MAPK,ERK in hippocampus of mouses in every group,and by the way of real-time PCR to detect the expression of RASmRNA?MAPKmRNA?ERKmRNA in hippocampus of mouses in every group,in order to abserve the effect on regulating and controlling of RAS-MAPK-ERK Signal conduction pathway in hippocampus of depression model mouses with Shuyu Prescription,and to probe its molecule mechanism of regulation on neuroplasticityResults:Experiment one:1.Open field test: Compared with rats in model group,march total distance,activity distance in center,duration of stay in center,traversing-times in center,average velocity in open field,and Stand number were markedly increased of the rats in Shuyu Prescription high-dose and medium-dose group(P<0.001,P<0.01,P<0.05);Compared with rats in model group,various indexes in open field test of the rats in Shuyu Prescription low-dose had no statistical significance,but had increasing trend.2.Sucrose preference test: Compared with rats in model group,sucrose preference coefficient were markedly increased of the rats in Shuyu Prescription high-dose and medium-dose group(P<0.01,P<0.05);Compared with rats in model group,sucrose preference coefficient of the rats in Shuyu Prescription low-dose had no statistical significance,but had increasing trend.3.The effect on the activity of related neurotrophic factor in cerebral cortex of depression model rats of Shuyu Prescription: Compared with rats in model group,the activity of NGF,BDNF,CREB in cerebral cortex were markedly increased of the rats in Shuyu Prescription high-dose and medium-dose group(P<0.001,P<0.01,P<0.05);Compared with rats in model group,the activity of NGF,BDNF,CREB in cerebral cortex of the rats in Shuyu Prescription low-dose had no statistical significance,buthad increasing trend.4.The effect on the express of RAS,MAPK,ERK in hippocampus of depression model rats of Shuyu Prescription: Compared with rats in model group,the express of RAS,MAPK,ERK in hippocampus were markedly increased of the rats in Shuyu Prescription high-dose and medium-dose group(P<0.001,P<0.01,P<0.05);Compared with rats in model group,the express of RAS,MAPK,ERK in hippocampus of the rats in Shuyu Prescription low-dose had no statistical significance,but had increasing trend.5.The effect on the express of gene of RAS-MAPK-ERK Signal conduction pathway in hippocampus of depression model rats of Shuyu Prescription: Compared with rats in model group,the express of RASmRNA,MAPKmRNA,ERKmRNA in hippocampus were markedly increased of the rats in Shuyu Prescription high-dose and medium-dose group(P<0.001,P<0.01,P<0.05);Compared with rats in model group,the express of RASmRNA,MAPKmRNA,ERKmRNA in hippocampus of the rats in Shuyu Prescription low-dose had no statistical significance,but had increasing trend.Experiment second:1.Open field test: Compared with mouses in model group,march total distance,activity distance in center,duration of stay in center,traversing-times in center,average velocity in open field,and Stand number were markedly increased of the mouses in Shuyu Prescription high-dose and medium-dose group(P<0.001,P<0.01,P<0.05);Compared with moudes in model group,various indexes in open field test of the mouses in Shuyu Prescription low-dose had no statistical significance,but had increasing trend.2.Elevated plus maze experiment: Compared with mouses in model group,total number of all arms and OT% were markedly increased of the mouses in Shuyu Prescription high-dose and medium-dose group(P<0.01,P<0.05);Compared with moudes in model group,various indexes in elevated plus maze experiment of the mouses in Shuyu Prescription low-dose had no statistical significance,but had increasing trend.3.Forced swimming test: Compared with mouses in model group,immobile time in forced swimming test were markedly decreased of the mouses in Shuyu Prescription high-dose and medium-dose group(P<0.01,P<0.05);Compared with moudes in model group,immobile time in forced swimming test of the mouses in Shuyu Prescription low-dose had no statistical significance,but had decreasing trend.4.The effect on the activity of related neurotrophic factor in cerebral cortex of depression model mouses of Shuyu Prescription: Compared with mouses in model group,the activity of NGF,BDNF,CREB in cerebral cortex were markedly increased of the mouses in Shuyu Prescription high-dose and medium-dose group(P<0.001,P<0.01,P<0.05);Compared with mouses in model group,the activity of NGF,BDNF,CREB in cerebral cortex of the mouses in Shuyu Prescription low-dose had no statistical significance,but had increasing trend.5.The effect on the express of RAS,MAPK,ERK in hippocampus of depression model mouses of Shuyu Prescription: Compared with mouses in model group,the express of RAS,MAPK,ERK in hippocampus were markedly increased of the mouses in Shuyu Prescription high-dose and medium-dose group(P<0.001,P<0.01,P<0.05);Compared with mouses in model group,the express of RAS,MAPK,ERK in hippocampus of the mouses in Shuyu Prescription low-dose had no statistical significance,but had increasing trend.6.The effect on the express of gene of RAS-MAPK-ERK Signal conduction pathway in hippocampus of depression model mouses of Shuyu Prescription:Compared with mouses in model group,the express of RASmRNA,MAPKmRNA,ERKmRNA in hippocampus were markedly increased of the mouses in Shuyu Prescription high-dose and medium-dose group(P<0.001,P<0.01,P<0.05);Compared with mouses in model group,the express of RASmRNA,MAPKmRNA,ERKmRNA in hippocampus of the mouses in Shuyu Prescription low-dose had no statistical significance,but had increasing trend.Conclusion: Shuyu Prescription could increase the independent activities instrange environment,their exploration of new environment and their ability to adapt to the environment of depressed animals;It could increase sucrose preference coefficient and regulate anhedonia caused by depression;It could increase the ability of depressed mices to explore novel environment and overcome their fear to some extent;It could increase the survival desire of depressed mices and shorten the time of desperate behavior;It could increase the activity of NGF,BDNF and CREB in cerebral cortical tissues of depressed animals,regulate the lack of neurotrophic substances in cerebral cortical tissues caused by depression,accelerate the growth and differentiation of nerve cells,slow down the apoptosis of nerve cells,and improve the state of nervous system damage;It could increase the expression of RAS,MAPK and ERK in depressed animals,regulate RAS-MAPK-ERK signal pathway conduction,and then regulate the neuroplasticity of depression and improve the state of nervous system damage.In conclusion,Shuyu Prescription could improve variety of symptoms of depression,and promoting neuronal plasticity by the way of impact brain nutrients content with regulating and controlling RAS-MAPK-ERK signal conduction pathway maybe was its mechanism. |
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