Intervention Of Shuyu Granule On Cognitive Dysfunction Of Depression Model Animals And Its Mechanism Of Neural Transduction Pathway

Objective: The experiment adopted two kinds of animal models,included chronic unpredicted stress stimulation combined with solitary induced depressive cognitive dysfunction animal model and corticosterone induced depressive cognitive dysfunction animal model,we used Open-field test and Morris water maze test to studying behavioral changes in animals in both models,content of PKA-CREB signaling pathway-associated protein factor in prefrontal cortex and hippocampus of animals.Methods:1.Establish a rat model of chronic unpredicted stress stimulation combined with solitary.According to the body weight,it was divided into blank control group,model group,positive drug group,Shuyu granule low dose group,Shuyu granule middle dose group,Shuyu granule high dose group,12 rats in each group were given the drug for 28 days after model establishment for 14 days.Observe the autonomous activities of the rats(Open-field test)and the ability of learnning and memory(Morris water maze test).The expressions of PRKACA mRNA,PRKACB mRNA,CREB mRNA and NGF mRNA in rat prefrontal cortex were detected by fluorescence PCR.The expressions of PKA,CREB,pCREB and NGF protein in rat prefrontal cortex were detected by immunohistochemistry and western blot.2.Establish a corticosterone-induced depression cognitive dysfunction C57 mouse model,according to body weight,then divided into blank control group,β-cyclodextrin group,model group,positive drug group,Shuyu granule low dose group,Shuyu granule middle dose group,Shuyu granule high dose group,10 mice in each group were given the drug for 28 days.Observe the autonomous activity of the mice(Open-field test)and the ability of learnning and memory(Morris water maze test).The expression of PRKACA mRNA,PRKACB mRNA,CREB mRNA and NGF mRNA in mouse prefrontal cortex was detected by fluorescence PCR.The expression of PKA,CREB,pCREB and NGF protein inmouse prefrontal cortex was detected by immunohistochemistry and western blot.Results:1.Behavioral results showed,compared with the blank control group,the autonomic activities of the model group decreased,and the ability of learnning and memory decreased.Compared with the model group,the self-activity of the animals in each drug group increased,and the ability of learnning and memory increased.2.Compared with the blank control group,the expression of PRKACA mRNA,PRKACB mRNA,CREB mRNA and NGF mRNA in the prefrontal cortex of the model group were decreased.Compared with the model group,the expression of PRKACA mRNA,PRKACB mRNA,CREB mRNA and NGF mRNA in the prefrontal cortex of each drug groups were increased.3.Compared with the blank control group,the expression of PKA,CREB,pCREB and NGF protein in the prefrontal cortex and hippocampus of the model group were decreased.Compared with the model group,the PKA,CREB,pCREB and NGF proteins in the prefrontal cortex and hippocampus of each drug groups were increased.Conclusion:1.Shuyu Granule has the effect of improving the behavior of animal models of cognitive dysfunction in depression,can improve the desperate behavior of animals in depression and improve the learning and memory ability of animals.2.Shuyu Granule can promote the expression of PRKACA mRNA,PRKACB mRNA,CREB mRNA and NGF mRNA in PKA-CREB signaling pathway and promote the expression of PKA,CREB,pCREB and NGF proteins.It is indicated that Shuyu granules can promote the expression of downstream neuronal factors and improve cognitive dysfunction of depression by activating PKA-CREB signaling pathway.