Study On The Effects And Mechanisms Of Wenyangyixin Therapy On Hippocampal Synaptic Plasticity In Coronary Heart Disease With Depression Mice

Coronary heart disease(CHD)with depression that is a disease with complex pathogenesis that seriously affects the physical and mental health of patients.There are problems with increasing incidence,low diagnosis rate,and lack of safe and effective treatment methods.Based on the pathogenesis characteristics of coronary heart disease with heart-yang deficiency,phlegm and blood stasis,and according to the traditional chinese medicine(TCM)theories of “heart governs blood vessels”,“heart regulates spirits” and“physical-psychological holistic theory”,Professor Cao Hong-xin proposed the use of Wenyang-Yixin therapy to treat CHD with depression.Abnormal BDNF level is one of the potential pathogenesis of CHD with depression,and it is also an important target for the treatment of CHD with depression.Based on the preliminary clinical and experimental research,this study further explored the mechanism of Wenyang-Yixin therapy based on regulating the BDNF/Trk B signaling pathway to improve hippocampal synaptic plasticity in CHD with depression through animal experiments.Objective: To investigate the effects of Wenyang-Yixin therapy on behavior,hippocampal CA1 region neurons and synaptic ultrastructure,synaptic plasticity-related proteins and gene expression in mice with coronary heart disease combined with depression,and to explore the effects of BDNF receptor Trk B inhibitor K252 a to explore the mechanism of Wenyang-Yixin therapy to improve hippocampal synaptic plasticity in CHD with depression provides a detailed scientific basis for the clinical treatment of CHD with depression.Methods: 1.A mouse model of CHD with depression was prepared by intraperitoneal injection of vitamin D3,lard gavage and high-fat feed combined with CUMS,The successfully modeled mice were randomly divided into model group(were given the same dose of purified water)and western medicine group(were given 2.6 mg/kg/d fluoxetine and 1.3 mg/kg/d atorvastatin calcium solution),Wenxinfang low-dose group(were given12.61g/kg/d Wenxinfang aqueous solution),Wenxinfang middle-dose group(were given 25.21g/kg/d Wenxinfang aqueous solution),Wenxinfang high-dose group(were given 50.42g/kg/d Wenxinfang).A total of 6 groups of mice were added to the blank group(gave the same dose of purified water).Detecting changes in mouse body weight,using Forced Swimming Test(FST),Open Field Test(OFT),and Elevated Plus Maze test(EPM)to detect depression behavior in mice;HE staining method was used to observe the pathological changes of mouse cardiomyocytes and aorta;Biochemical methods was used to detect serum lipid levels in mice;Nissl staining and HE staining methods were used to observe the morphological changes of mouse hippocampal CA1 region neurons;electron microscopy was used to detect the ultrastructure of mouse hippocampal CA1 region synapses;Western Blot method was used to detect the protein expression of mouse hippocampus SYN,GAP43,PSD-95,BDNF,Trk B,p-Akt/Akt,p-ERK/ERK,p-CREB/CREB;RT-PCR method was used to detect mouse hippocampal SYN,GAP43,PSD-95,BDNF,Trk B,Akt,ERK,CREB gene levels.2.Using the BDNF receptor Trk B inhibitor K252 a,Western Blot method was used to detect the protein expression levels of mouse hippocampus SYN,GAP43,PSD-95,BDNF,p-Akt/Akt,p-ERK/ERK,p-CREB/CREB.Results: 1.The body weight of mice in the model group decreased significantly(p<0.01);the immobility time of FST increased significantly(p<0.01);the level of HDL-C decreased(P<0.05),and the levels of TC,TG,and LDL-C increased significantly(P<0.01);HE staining showed that myocardial cells were arranged disorderly and loosely,fibrosis was severe,and plaques appeared in arteries.2.Wenyang-Yixin therapy can reduce the immobility time of FST of model mice(p<0.05),increase the OE% value and OT% value of EPM(p<0.01),and increase the number of times that PFT enters the central area and the center District activity time(p<0.05).3.Wenyang-Yixin therapy can increase the number of hippocampal CA1 region neurons in model mice,reduce the loss of Nissl bodies,and improve hippocampal synaptic plasticity.4.Wenyang-Yixin therapy can improve hippocampal SYN,GAP43,PSD-95,BDNF,Trk B,Akt,ERK,CREB m RNA expression in model mice(p<0.01);increase hippocampus SYN,GAP43,PSD-95,BDNF,Trk B,p-Akt/Akt,p-ERK/ERK,p-CREB/CREB protein expression(p<0.01).5.After the Trk B inhibitor K252 a was used,Wenyang-Yixin therapy can not increase the hippocampal BDNF,Trk B,p-Akt/Akt,p-ERK/ERK,p-CREB/CREB,SYN,GAP43,PSD-95 protein expression in model mice(p<0.01).Conclusions : 1.The method of intraperitoneal injection of vitamin D3,lard gavage and high-fat feed combined with CUMS can successfully prepare a mouse model of CHD with depression.2.Wenyang-Yixin therapy can increase the expression of hippocampal BDNF,Trk B,Akt,ERK,CREB genes and proteins,and increase the expression of hippocampal synaptic plasticity-related proteins SYN,GAP-43,PSD-95,and exert a protective effect on hippocampal neuron synaptic plasticity.3.Wenyang-Yixin therapy may improve the synaptic plasticity of hippocampus in mice with CHD depression by regulating the BDNF/Trk B signaling pathway,and exert a therapeutic effect on CHD with depression.