Medication Rules And Network Pharmacology Study Of Professor Xing Yanwei On Treatment For Heart-Yang Deficiency Type Of Bradyarrhythmia

This thesis is divided into two parts,including literature reviews and clinical studies.The literature reviews introduce the current treatment status of bradyarrhythmia(BA)in modern medicine and the progress of research about bradyarrhythmia at the molecular level.In addition,through the literature search of bradyarrhythmia,we summarized the current common herbal formulas and Chinese patent medicines for the treatment of Yang deficiency type of BA.as well as the experiences of some famous and old Chinese medicine practitioners.In terms of clinical researchs,we conducted data mining of outpatient cases of BA treated by Prof.Xing Yanwei,and mined the medication pattern and core experience prescription of Prof.Xing Yanwei’s treatmentXinhuankang Granules.A network pharmacological analysis of the core empirical prescriptions was conducted to explore the possible effective targets and pathways of Xinhuankang Granules for the treatment of BA,in order to providing the molecular basis for treatment and drug discovery..Objective1.Using the data mining software of "TCM inheritance computing platform V3.0",we analyzed the prescription data of Professor Xing Yanwei’s treatment of patients with BA of deficiency of heart-yang type,explored the clinical medication pattern,Professor Xing Yanwei’s dialectical thinking and medication characteristics,and summarized the core experience prescription-Xinhuankang Granules.2.The network pharmacology study was used to explore the possible effective targets and pathways of Xinhuankang Granules for the treatment of BA,providing the molecular basis for treatment and drug discovery.Methods1.The medical records and prescriptions of patients with BA who attended the clinic of Dr.Xing Yanwei,Chief Physician of Guanganmen Hospital from January 2019 to May 2022 and whose syndrome differentiation was based on the evidence of deficiency of heart yang.The eligible medical records were screened according to the inclusion and exclusion criteria,and the medical records were standardized and entered into the data mining software "TCM Heritage Computing Platform V3.0" for analysis.The data were analyzed in terms of the basic information of the medical records,the four qi and five flavors of the medicine and the attribution of meridians,and the core prescriptions of Professor Xing Yanwei for the treatment of BA of the deficiency of heart-yang type based on the clustering algorithm of the data mining software.2.The six drugs of the core empirical prescription,Xinhuankang Granules,were obtained from the TCMSP platform by data mining to obtain the active ingredients and candidate targets.The obtained drug components-candidate targets were mapped with the candidate targets of BA,and the intersection was taken to obtain 70 key targets.Using CytoscapeV3.6.0 software,we obtained the network diagram of "drug-active ingredient-disease-target" of Xinhuankang Granules;constructed PPI network diagram;performed KEGG signaling pathway analysis and GO enrichment analysis.Results1.The study finally included a total of 206 cases and 518 consultations of BA patients with deficiency of heart-yang type,and a total of 518 prescriptions were obtained,which contained a total of 355 flavors of Chinese medicine.The age of patients with deficiency of heart-yang type of BA was on the rise,and the high prevalence age was concentrated in 58-77 years old.The 25 most commonly used drugs were Hosin.Ephedra,Dihuang,Huang Jing,Radix et Rhizoma,Zhi Mu,Fried Sour Date Palm,Ginger,Dry Ginger,Medlar,Radix Aromaticus,Hopi Bark,Cinnamon,Epimedium,Schisandra,White Peony,Mother of Pearl,Fructus Fructus,Bacopa monniera,Gangsong,Astragalus,Muxiang,Codonopsis,Poria,Sandalwood,etc..Medications used The medicinal properties were mostly warming,and the medicinal tastes were mostly pungent,sweet and bitter.The drug meridians were higher in spleen,lung,liver,kidney,stomach and heart meridians,accounting for 86%of the total weight.Based on the association rule analysis,the seven most commonly used drug pairs were obtained,namely,Hosin and Huangjing,Hosin and Radix et Rhizoma,Hosin and Zhiwu,Dihuang and Huangjing,Radix et Rhizoma,Hosin and Ephedra,Hosin and Ephedra,Hosin and Dihuang.Meanwhile,based on the clustering algorithm,the core empirical prescription with the highest frequency of use,Xinhuankang Granules(Hosin,Ephedra,Radix et Rhizoma,Radix et Rhizoma,Rhizoma Polygonati,Rhizoma Polygonati),was mined.2.The results of the network pharmacology study suggest that the action targets of Xinhuankang Granules for the treatment of BA mainly include 70 key targets such as PTGS2,SCN5A,ADRB2,AR,PPARG,ESR1,NOS2,etc..Among them,there are 44 active ingredients,mainly quercetin,lignocaine,kaempferol,naringenin,etc..Possible signaling pathways for BA treatment with Xinhuankang Granules include cancer signaling pathways,fluid shear stress and atherosclerosis pathways,AGERAGE signaling pathways in diabetic complications,lipid and atherosclerosis pathways,proteoglycan pathways in cancer,and PI3K-Akt signaling pathways,involving biological processes such as inflammation,immunity and oxidative stress.Discussions1.Professor Xing Yanwei summarized the characteristics of heart-yang deficiency causing the disease in his years of clinical practice in treating BA,and the treatment excels in the method of warming yang.Based on the results of the overall prescription data mining and the analysis of the core prescriptions,we summarized the effective treatment of deficiency of heart-yang type BA with the Chinese herbal medicine compound Xinhuankang granules,in which the drugs in the compound include Hosin,Radix et Rhizoma Polygonati,Huangjing,Ephedra,Dihuang and Zhi Mu.Among them,Ephedra is the ruler and Radix et Rhizoma is the minister,taking the warmth of the drug to supplement the deficiency of heart yang.2.According to the results of the network pharmacology study,the diversity of targets and the complexity of pathways involved in the treatment of heart-yang deficiency type of BA with Xinhuankang Granules can be seen.The most likely targets of Xinhuankang Granules for the treatment of BA include PTGS2,SCN5A,ADRB2,AR,PPARG,ESR1,NOS2,etc..These targets involve complex pathway actions and are related to biological processes such as immunity,inflammation and oxidative stress.The results of the network pharmacology studies provide the basis for the molecular structure level of drug development.