Molecular Mechanism And Clinical Study Of Didang Tongmai Decoction In The Treatment Of Deep Venous Thrombosis

Objective: To explore the molecular mechanism of Didang Tongmai Decoction on deep venous thrombosis(DVT)by using the method of network pharmacology,and to observe the clinical effect of Didang Tongmai Decoction in the treatment of DVT.Methods: In Study 1,TCMSP database,BATMAN database,CNKI,Pub Med database and COREMINE database were used to search the effective components of various traditional Chinese medicines in Didang Tongmai Decoction and predict action targets.The targets of DVT were obtained through Gene Cards database,CTD database and OMIM database,and the intersection key targets were obtained by mapping the component action targets with the disease targets.Using STRING database to establish protein-protein interaction(PPI)network and screen core targets.The network diagram of traditional Chinese medicine-component-target-disease was constructed to obtain the core components by using Cytoscape 3.7.2 software.And the Clue Go plug-in was used to analyze the enrichment of KEGG pathway of Didang Tongmai Decoction in the treatment of DVT.Using Auto Dock Vina program to verify the molecular docking of core active components and targets.In Study 2,60 patients with DVT who met the criteria were randomly divided into experimental group and control group,with 30 cases in each group.The general data(gender,age,course of disease,location of onset,clinical classification and inducing factors)of the two groups were collected,and the symptoms and signs were recorded and scored according to the traditional Chinese medicine(TCM)syndrome score table.The control group was given routine basic treatment,and the experimental group was given Didang Tongmai Decoction on the basis of the control group.The clinical efficacy and TCM syndrome improvement of the two groups were observed 14 days after treatment,and the C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),mean platelet volume(MPV),platelet distribution width(PDW),large platelet ratio(P-LCR),fibrinogen(FIB),D-dimer,antithrombin III(AT-III)activity,protein C(PC)activity,lupus anticoagulant(LA)screening ratio,fibrin monomer(FM),von Willebrand factor antigen(VWF: Ag),thromboelastogram(TEG)were compared before and after treatment,and the venous patency rate of the two groups after 14 days of treatment was calculated.Results: Study 1 showed that: A total of 708 potential targets and 1542 DVT targets of active components in Didang Tongmai Decoction were obtained.The core targets obtained by PPI network analysis were albumin(ALB),interleukin-6(IL-6),tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA)and fibronectin1(FN1).The core components obtained by traditional Chinese medicine-component-target-disease network analysis are hirudins,quercetin,β-sitosterol,arachidonic acid,isorhamnetin.109 pathways were obtained by KEGG analysis.Molecular docking showed that the binding ability between the core component and the target was good.Study 2 showed that: The total effective rate and obvious healing rate of patients in the experimental group were higher than those in the control group(P<0.05).Compared with before treatment,the score of TCM syndrome in the two groups decreased significantly 14 days after treatment(P<0.01),and the score of TCM syndrome in experimental group was lower than that in control group(P<0.05).CRP,TNF-α,FIB,D-dimer,LA screening ratio,FM,v WF: Ag,α angle,MA value,and CI value of two groups of patients 14 days after treatment were lower than before treatment(P<0.05,P<0.01),AT-III activity,PC activity,R value,and K value were increased compared with before treatment(P<0.01).CRP,TNF-α,FIB,D-dimer,and α angle of the experimental group were lower than that of the control group 14 days after treatment(P<0.05,P<0.01),AT-III activity,PC activity,R value,and K value were higher than those in the control group(P<0.05,P<0.01).The venous patency rate in experimental group was significantly higher than that in control group(P<0.01).During treatment,no obvious adverse reaction events such as liver and kidney function impairment and allergies were found in both groups of patients.Conclusion: 1.Hirudins,quercetin β-sitosterol,arachidonic acid and isorhamnetin may exert their anti-inflammatory,anticoagulant and inhibitory effects on platelet activation by acting on the core targets ALB,IL-6,TNF,VEGFA and FN1,and participating in TNF,PI3 KAkt,TLRs,MAPK,AGE-RAGE,platelet activation,NLR,CLRs and other signaling pathways to achieve the purpose of treating DVT.2.Didang Tongmai Decoction can effectively improve the symptoms and signs of patients with DVT,reduce the inflammatory response,improve the activity of AT-III and PC,reduce the level and function of coagulation factors,improve the hypercoagulable state of blood and promote venous recanalization.