Clinical Evaluation And Mechanism Of Qingtan Huayu Recipe In The Treatment Of Stable Coronary Heart Disease With Phlegm-Heat And Blood Stasis Syndrome

Objective1.To evaluate the clinical efficacy and safety of Qingtan Huayu Decoction in the treatment of stable coronary heart disease with phlegm-heat and blood stasis syndrome.2.To explore the effect of Qingtan Huayu Decoction on vascular endothelial function in patients with stable coronary heart disease with phlegm-heat stasis syndrome.3.Using network pharmacology to analyze the mechanism of Qingtan Huayu Decoction in the treatment of stable coronary heart disease.Methods1.Sixty patients with stable coronary heart disease with phlegm-heat and blood stasis syndrome were randomly divided into treatment group and control group,with 30 cases in each group.The treatment course of both groups was 10±3 days.The two groups both kept the original western medicine treatment unchanged,and the treatment group was treated with Qingtan Huayu Decoction on the basis of the original treatment plan unchanged.The general physical examination,angina pectoris symptom score,Seattle angina pectoris scale score,traditional Chinese medicine（TCM）syndrome score,routine echocardiography,brachial artery flow-mediated vasodilation function,endothelin-1,nitric oxide,blood lipid,safety index and adverse reactions were recorded before and after treatment.2.The active components and action targets of Qingtan Huayu Decoction were screened from the TCMSP,and stable coronary heart disease targets were screened based on Drugbank,TTD,Dis Ge NET and NCBI databases.Disease targets and drug targets were analyzed by Venn,and their common targets were screened.Using STRING database to construct Protein-protein interaction network.The GO function enrichment and KEGG pathway enrichment analysis of the common targets were carried out through DAVID（6.8）database,and the network of"traditional Chinese medicine-active ingredient-key target-disease"was constructed by Cytoscape3.6.0 to predict the mechanism of Qingtan Huayu Decoction in the treatment of stable coronary heart disease.Results1.General data comparison A total of 60 patients were enrolled,of which 2 patients were excluded,1 case in the treatment group,1 case in the control group,and 0 cases dropped out.Finally,we included 58 patients,29 in each group.There was no difference in blood pressure,heart rate,waistline,exercise,dietary preference,past medical history,routine use of western medicine and other baseline data between the two groups.2.Evaluation of therapeutic effect（1）scale score（1）Angina pectoris symptom scoreAfter treatment,the angina pectoris symptom score in the treatment group was lower than that before treatment(P_组间<0.001),and the net difference angina pectoris symptom score in the treatment group was 2.06 points（95 CI:1.51～2.63 points）.There was no significant change in the symptom score of angina pectoris in the control group after treatment(P_组内=0.326),but the angina pectoris symptom score in the treatment group was lower than that in the control group(P_组间=0.019).（2）Seattle Angina scale scoreThe scores of physical activity limitation,angina pectoris stability,angina pectoris attack,treatment satisfaction and disease awareness in the treatment group were significantly higher than those before treatment in the treatment group（P<0.01）.There was no significant difference in the control group after treatment in the(P_组内>0.05).After treatment,the physical activity limitation symptom score,angina stability score,and treatment satisfaction score were significantly higher in the treatment group than the control group(all P_组间<0.01),and the angina pectoris episode score and disease awareness score were higher in the control group(all P_组间<0.05).（3）TCM syndrome scoreAfter treatment,the TCM syndrome score of the treatment group was lower than that of the previous group(P_组内<0.001),and the net difference TCM syndrome score of the treatment group was 16.17 points（95 CI:12.72～19.62 points）.There was no significant difference in TCM syndrome score in the control group before and after treatment(P_组内=0.108).After treatment,the TCM syndrome score in the treatment group was lower than that in the control group(P_组间=0.004).（2）Blood lipid index.There was no obvious difference in blood lipids（triglyceride,total cholesterol,high density lipoprotein cholesterol,low density lipoprotein cholesterol,very low density lipoprotein cholesterol）between the two groups before and after treatment.before and after treatment in the two groups(all P_组内>0.05,all P_组间>0.05).（3）Brachial artery flow-mediated vasodilation（FMD）.The FMD of the treatment group was higher after treatment than that before treatment(P_组内<0.01),and the FMD of the control group did not change significantly after treatment（P>0.05）.There was a statistical difference in FMD between the two groups after treatment（P<0.05）.（4）Cardiac color ultrasound index.Before and after treatment,the two groups of patients have no significant difference in left ventricular end-diastolic diameter,left ventricular end-systolic diameter,left atrial diameter,right ventricular diameter,left ventricular wall thickness,interventricular septum,left ventricular stroke volume,minute output,cardiac index,ejection fraction and left ventricular short-axis shortening between the two groups before and after treatment(P_组内>0.05,P_组间>0.05).（5）Nitric oxide and endothelin-1There was no significant difference between the two groups of patients before treatment between nitric oxide and endothelin-1 groups(P_组间=0.630,P_组间=0.565).The level of nitric oxide after treatment in the treatment group was higher than that before treatment(P_组内<0.001),the net difference in nitric oxide concentration within the group was-10.77 uml/L（95%CI:-15.33～-6.19 uml/L）,and the endothelin-1 after treatment in the treatment group-1level was significantly lower than before treatment(P_组内<0.001),the net difference within the group endothelin-1 concentration was 3.00 ng/L（95%CI:-5.71～-0.29 ng/L）,the control group had a higher nitric oxide level before and after treatment.There was no statistical difference between the groups before treatment(P_组内=0.138),and the level of endothelin-1 in the control group after treatment was higher than before treatment(P_组内=0.031).After treatment,the level of nitric oxide in the treatment group was higher than that in the control group(P_组间<0.001),and the level of endothelin-1 in the treatment group was lower than that in the control group(P_组间=0.001).（6）Safety evaluationThere was no significant difference in blood pressure,heart rate,blood routine,electrolytes,liver and kidney function between the two groups before and after treatment.(all P_组内>0.05all P_组间>0.05).There was no significant difference in the incidence of adverse events between the two groups during the study period(all P_组间>0.05).3.Action mechanism101 active components and 253 corresponding targets of Qingtan Huayu recipe were screened by TCMSP database,and 1104 targets related to stable coronary heart disease were obtained based on Drugbank,TTD,Dis Ge NET and NCBI database,and 112 targets of Qingtan Huayu recipe in the treatment of stable coronary heart disease were obtained by the intersection of the two databases.GO functional enrichment analysis showed that there are 640 biological processes,including cell proliferation and apoptosis,inflammatory reaction,oxidative stress,hormone secretion,NO synthesis,substance metabolism and other biological processes,including enzymes,proteins,cytokines,receptors,transcription factors,hormones and other substances.KEGG pathway enrichment analysis showed that there were 108 signal pathways,and more targets were enriched on HIF-1 signaling pathway,PI3K-Akt signaling pathway,Toll-like receptor signaling pathway,c GMP-PKG signaling pathway and other signal pathways.Conclusion1.Qingtan Huayu Decoction can effectively improve the clinical symptoms of patients with stable coronary heart disease with phlegm-heat and blood stasis syndrome,improve quality of life,and is safe.2.Qingtan Huayu Decoction can effectively protect vascular endothelial function in patients with stable coronary heart disease with phlegm-heat and blood stasis syndrome,which is one of the possible mechanisms for clinical treatment of stable coronary heart disease.3.Qingtan Huayu Decoction may regulate PI3K-Akt signaling pathway,c GMP-PKG signaling pathway and other signal pathways to treat stable coronary heart disease by acting on key targets such as TNF,AKT1,IL-6,MAPK3,MAPK8,VEGFA,FOS and so on.