Mongolian Medicine Nutmeg Wuwei Pills On CUMS Rats Regulation Mechanism Of Hippocampal CAMP-PKA Signaling Pathway

Objective:To observe the regulatory mechanism of Mongolian medicine Rou Kou Wu Wei Wan on cAMP-PKA signaling pathway in hippocampus of CUMS rats.Method:After 100 male SD rats(weight 180-200g)were adaptively fed for 1 week,they were randomly divided into 10 groups according to their body weight.Each group consisted of 10 rats.A blank group,a model group,and a positive drug group(with fluoxetine 3.6 were given)mg/kg),Mongolian medicine Nutmeg Wuwei Pills in high,medium and low dose groups(respectively giving Nutmeg Wuwei Pills 1.6g/kg,0.8g/kg,0.4g/kg),H-89 group(administer blocker H-89 0.05mg/kg),H-89+fluoxetine group(administer blocker H-89 0.05mg/kg+fluoxetine hydrochloride 3.6mg/kg),H-89+Mongolian nutmeg Wuwei pills Dose group(blocker H-89 0.05mg/kg+Nuokou Wuwei Pills 1.6g/kg,0.8g/kg respectively).The rats in the normal group were fed with 5 rats per cage.They were fed and fed normally without any stimulation.The rats in the other groups were fed in a single cage and given different stimulation.After the modeling was started,each group was given the corresponding drugs by intragastric administration every day,and the blank group and model group were given the same amount of normal saline for 28 days.The blocking agent H-89 was injected into the tail vein every week.Modeling method:The model of depression model rats was modeled with orphanage and chronic mild unpredictable sexual stimulation.Test indicators and methods:After the model is built,according to the 1%sucrose consumption test(SPF),body weight change,tail suspension test(TST),Morris water maze learning and memory test,open box test(Open-field)And other methods to evaluate the model and measure the behavioral changes of depression model rats.Immunohistochemistry was used to detect the expression of CREB and BDNA proteins in hippocampus,and ELISA was used to detect the content of AC,cAMP and PKA in hippocampus.Results:1.Effect on the behavior of rats:After the experiment,compared with the blank group,the model group 1%sucrose consumption,body weight changes,open box experiment horizontal crossing number,and the number of erections were significantly reduced(P<0.01,P<0.05),significantly increased the immobility time of tail suspension(P<0.01,P<0.05);1%sucrose consumption,weight change,open box experiment level crossing of rats in the positive drug group,Mongolian medicine high and middle dose groups The number of grids and the number of erections were significantly higher than those in the model group(P<0.01,P<0.05),and the immobility time of the tail was significantly reduced(P<0.05).There was no significant difference between the low-dose Mongolian medicine group;the positive medicine group and H-89+Fluoxetine group,Mongolian medicine high and medium dose group were compared with H-89+Mongolian medicine high+medium dose group,1%sucrose consumption,weight change,open box experiment horizontal crossing grid number,number of erections and tail suspension There were differences in time,but no statistical significance.It means that the curiosity and exploration behavior of the rats in the model group are reduced,and the sense of pleasure is lacking.Mongolian medicine Rou Kou Wu Wei Wan can improve the behavioral expression of rats.2.The effect on the content of AC,cAMP and PKA in the hippocampus of rats:Compared with the blank group,the content of AC,cAMP and PKA in the model group was significantly reduced(P<0.01,P<0.05);compared with the model group,the positive drug The levels of AC,cAMP and PKA in the hippocampus of rats in the high-and middle-dose group of Mongolian medicine and nutmeg Wuwei pill increased(P<0.01,P<0.05);the low-dose group of Mongolian medicine nutmeg and Wuwei had no statistical significance;Compared with the positive drug group,there was no significant change in the AC and cAMP contents in the hippocampus of the H-89+fluoxetine group;the PKA content had a downward trend;compared with the Mongolian medicine Nutmeg Wuweiwan high and medium dose groups,H-89+The content of AC and cAMP in the hippocampus of the Mongolian medicine Roukou Wuwei Pills in the high and middle dose groups did not change significantly;the PKA content was significantly reduced(P<0.05).3.Effect on the expression of CREB and BDNF in the rat hippocampus:Compared with the blank group,the expression of CREB and BDNF in the model group was significantly decreased(P<0.01,P<0.05);compared with the model group,the positive drug group and the Mongolian medicine meat The expression of CREB and BDNF in the hippocampus of the high-and middle-dose groups of Koowu Pills was significantly increased(P<0.01,P<0.05);the low-dose group of Mongolian nutmeg Wuwei had no statistical significance(p>0;Compared with the high-dose group,the expressions of CREB and BDNF in the hippocampus of H-89+Mongolian medicine Luokou Wuweiwan high-dose group showed a downward trend.Conclusion:1.Mongolian medicine Rouguo Wuwei Pills changed the behavioral expression of CUMS rats,improved the curiosity of the external environment of the rats,reduced the exploration behavior,and lost the pleasure.2.Mongolian medicine Rou Kou Wu Wei Wan can increase the content of AC,cAMP and PKA in hippocampus of CUMS rats,and its effect may be related to the activation of cAMP-PKA signal pathway by Rou Kou Wu Wei Wan.3.Mongolian medicine Rouguo Wuwei Pills changes the expression of CREB and BDNF protein in the hippocampus by regulating cAMP-PKA signaling pathway in the brain of CUMS rats,which may be one of the important mechanism of action of Rouguo Wuwei Pills in the treatment of depression.