Clinical And Network Pharmacological Study Of Shenzhi Tongxin Capsule In The Treatment Of Dilated Cardiomyopathy With Qi Deficiency And Blood Stasis Syndrome

Objective:To observe the clinical efficacy and safety of Shenzhi Tongxin Capsules in the treatment of dilated cardiomyopathy patients with qi deficiency and blood stasis syndrome,study its network pharmacological mechanism to provide clinical basis and theoretical support for the treatment and delay of the process of dilated cardiomyopathy with qi deficiency and blood stasis syndrome.Methods:1.Clinical research: A total of 60 patients who met the inclusion criteria were collected and randomly divided into the traditional Chinese medicine(TCM)intervention group and the control group,30 in each group.The control group was given basic western medicine treatment,while the TCM intervention group was given Shenzhi Tongxin Capsule plus western medicine basic treatment,and the observation period was 4 weeks.TCM syndrome scores,cardiac function classification,6-minute walking distance,blood(NT-pro BNP,CRP,Scr,BUA)levels,echocardiographic indexes(including FS,LVEF,LVEDd)and Kansas City Cardiomyopathy Quality of Life(KCCQ-12)Score were evaluated to compare the two groups’ changes.2.Network pharmacology research: The active ingredients and potential targets of Shenzhi Tongxin Capsules in the treatment of DCM were screened by TCMSP,BATMAN-TCM,Gene Cards,Uniprot and other databases,as well as Venny platform.Using Cytoscape3.7.2 software and STRING database,the visual network diagram and protein-protein interaction network diagram of "Shenzhi Tongxin Capsule-Component-Target-Dilated Cardiomyopathy" were constructed,and the core targets were screened out.The resulting intersection targets were analyzed for GO function and KEGG pathway enrichment analysis using the DAVID database platform,and then were visually analyzed by the Omic Share cloud platform.Bio GPS,Gnencards,Dis Ge NET databases were used to obtain the tissue distribution,subcellular distribution and protein attribution information of core targets.Using websites and software such as Pub Chem,Chem3 D,PDB,Py Mol and Auto Dock Tools,the core targets and main compound components were molecularly docked.Results:1.Clinical research: The data of the two groups before treatment were balanced and comparable(P>0.05).Judging from the effect after treatment,all indexes in the TCM intervention group were significantly improved after treatment compared with those before treatment(P<0.05).TCM syndrome integral,therapeutic effect of TCM symptom score,the efficacy of cardiac function classification,echocardiographic indicators(including LVEF,LVEDd),blood(NT-pro BNP,hs-CRP,Scr,BUA)level,6-minute walking distance,and KCCQ-12 score were compared with the control group,the differences were statistically significant(P<0.05).Although FS was found to differ little from the control group in the post-treatment comparison(P>0.05),the difference between the two groups before and after treatment showed that the TCM intervention group still had advantages(P<0.05).2.Network pharmacology research: A total of 136 potential active ingredients of Shenzhi Tongxin Capsules were screened,and294 intersecting targets were obtained.Among them,stigmasterol,crocus acid,β-sitosterol,quercetin and other components have higher degrees.The top 6 core targets screened were INS,AKT1,ALB,IL6,VEGFA,and TNF.A total of 514 GO biological functions and 123 KEGG pathways were obtained by enrichment analysis.From the GO function,KEGG pathway and the distribution chart of tissue,subcellular and protein,Shenzhi Tongxin capsules may operate in the extracellular space,plasma membrane,endoplasmic reticulum,nucleus,Golgi apparatus,and membrane rafts,through processes like aging,response to hypoxia,ethanol,drug and binding of drug,flavin adenine dinucleotide,enzyme and so on,with the help of c AMP signaling,calcium signaling,neuroactive ligand-receptor interaction,non-alcoholic fatty liver disease(NAFLD)and other signaling pathways,and the above results of molecular docking were good.Conclusions:1.Shenzhi Tongxin Capsules can effectively improve the clinical symptoms,laboratory indicators and quality of life of patients with DCM,with high safety and worthy of clinical promotion.2.Network pharmacology and molecular docking studies have revealed that Shenzhi Tongxin Capsule may be composed of multiple components including stigmasterol,crocus acid,β-sitosterol and quercetin,Multiple targets,represented by INS,AKT1,ALB,IL6,VEGFA,and TNF,involving c AMP signaling pathway,calcium signaling pathway,neuroactive ligand-receptor interaction,non-alcoholic fatty liver disease(NAFLD)and other signaling pathways,after the direct or indirect action of multiple tissues,subcells,and proteins,regulating human immunity,repairing of the vascular endothelial cells,combating the oxidative stress,inhibiting autophagy,apoptosis and remodeling of extracellular matrix to play a role in the teatment of dilated cardiomyopathy.