Study On Mechanism Of Atherosclerosis Comorbid With Depression Treated By Guanxin Ⅱ Formula

Background and proposeCoronary heart disease is the main cause of death in the world.Depression is an independent risk factor for the onset and progression of coronary heart disease.It often leads to the occurrence of critical acute coronary disease,increases patient mortality,reduces the effect of drug treatment and quality of life,and increase medical burden.Research methodsIn the experiment,ultra high performance liquid chromatography(UPLC)method was used to detect the chemical constituents contained in Guanxin Ⅱ decoction,and further highperformance liquid chromatography tandem mass spectrometry analysis was used to elucidate the components of C57BL/6 mice absorbed into the blood after oral administration of Guanxin Ⅱ.In the active components of the hippocampus and prefrontal cortex target organs,two analytical tests confirmed that ferulic acid is one of the main chemical components of Guanxin Ⅱ that is absorbed into the blood and into the brain;ApoE-/-mice were fed with a high-fat diet to establish an animal model of atherosclerosis.Serum lipids and inflammatory factors were detected.Oil red O staining and HE staining were used to determine plaque formation area andvascular endothelial tissue damage.Depressionassociated behavioral evaluations were performed concurrently in CHD model mice.RNA-seq sequencing was used to analyze comorbidity models for differentially expressed genes.The differentially expressed genes were analyzed by GO database annotation and KEGG enrichment in the biological database.PPI protein interaction network The functional analysis of differentially expressed gene regulatory proteins was performed to establish the evaluation criteria for the model of coronary heart disease co-depression mice,on this basis,the efficacy of GXⅡ decoction and its main absorption component ferulic acid in the treatment of coronary heart disease co-depression mouse models was studied.MechanismResultsThe results showed that ferulic acid,danshensu and hydroxysafflor yellow A are the main components of GXⅡ decoction.Ferulic acid is low in GXⅡ decoction,but it can be absorbed into the blood in large quantities and in target organs.Enrichment(hippocampus and prefrontal cortex).High-fat diet-fed ApoE-/-mice established coronary heart disease model,there is a certain degree of cognitive depressive disorder;coronary heart Ⅱ group,ferulic acid group,and the model group compared to the control group,can significantly reduce Blood lipid levels in mice reduced circulating blood inflammation,reduced atherosclerotic plaque area and endometrial tissue damage in the thoracic aorta;partially improved cognitive depressive disorder.In in vitro cell experiments,ferulic acid activates the NF-κB/NLRP3 inflammasome pathway and exerts its effect of reducing ox-LDL-induced foaming of RAW264.7 cells,thus partially representing the anti-atherosclerotic effect of GXⅡ formula.mechanism.Conclusion and significanceIn this study,UPLC detection of the main components of the formula,HPLC-MSMS to further detect the absorption of prescription into the blood and target organ distribution,reverse the search for the possible prescription of the main efficacy components;This study evaluated cognitive impairment in a classic mouse model of coronary heart disease.RNA-seq gene expression profiling was needed to find genes related to coronary heart disease depression,and GXⅡ decoction and its main absorption components were further studied.Effects of Acid on Pharmacodynamic Mechanism of Coronary Heart Disease Co-morbid Depression in Mouse Model.The results of this experiment provide a model for the further study of coronary heart disease depression comorbidity and evaluation methods;inverse need to find the prescription absorbed into the blood and the main components in the target organs,compared the main absorption of the ingredients and the role of the mother’s pharmacodynamics,Through the elucidation of the pharmacological mechanisms of the main absorption components on cell molecules,the mechanism of the maternal efficacy can be further clarified.