Study On Medication Rule And Network Pharmacology Of Type 2 Diabetes Mellitus Complicated With Obesity With Phlegm And Blood Stasis Syndrome

Objective:1.Applicating data mining to analyze the medication law of surpe-rvisor in treating type 2 diabetes mellitus complicated with obesity with phlegm and blood stasis syndrome,and summarize the clinical experie-nce of surpervisor.2.To explore the mechanism of the core drugs for treating type 2diabetes mellitus complicated with obesity with phlegm and blood stasis by network pharmacology.Methods:1.Collecting the first effective case data of patients with type 2 diabetes complicated with obesity who were diagnosed and treated by their surpervisor in the Endocrine Inpatient Department of the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine from October 2018 to October 2021.Standardizing the case data such as symptoms,tongue pulse and Chinese medicine names and so on.Applicating the traditional Chinese medicine inheritance computing platform V3.0 to establish a databasefor data mining.excavating the surpervisor’s treatment of type 2 diabetes complicated with obesity through statistical analysis,prescription analysis,association rules and cluster analysis.3.The core drugs of type 2 diabetes mellitus complicated with obesity with phlegm and blood stasis syndrome were analyzed by network pharmacology.The compounds with effective active ingredients were screened out by TCMSP database,and their corresponding protein targets were collected;The gene targets of diseases were searched in Gene Cards,Dis Ge NET and OMIO disease databases,and the intersection targets of drug protein targets and disease gene targets were obtained.The intersection target is imported into Cytoscape to construct a "drug-component-target" network,and the core target is obtained.The core target is imported into STRIN database to construct PPI network,and visual analysis is carried out.The enrichment analysis of GO and KEGG was carried out by using microbial website,and its mechanism was discussed.Results:1.148 cases were finally included in this study,including 87 males,accounting for 59% of the total number,and 61 females,accounting for 41%of the total number.The onset age was more than 60 years old(39%)and51-60 years old(34%).The oldest was 88 years old and the youngest was 20 years old.2.Among the cases included in this study,purple tongue appeared the most frequently,with a frequency of 90 times;White thick greasy coating appeared most frequently,with the frequency of 60 times.The most frequent pulse condition is heavy and astringent pulse,with a frequency of 82 times.There are 82 symptoms in symptom statistics,and the top 7 high-frequency symptoms are abdominal enlargement,dry,fatigue,insomnia,frequent urination,blurred vision and yellow urine.3.In the included cases,159 kinds of traditional Chinese medicines were used,and 10 kinds of medicines were used with frequency ≥60 times.Among them,the top 6 drugs in the frequency of use are Coptidis Rhizoma,Astragali Radix,Poria,Salvia Miltiorrhiza Radix,Chuanxiong Rhizoma and Pericarpium Citri Tangerinae in turn.The statistical results of the four gases of drugs are ranked as warm,cold,flat,cool and hot from high to low;The statistical results of the five flavors rank from high to low as sweet,bitter,pungent,salty and sour;The statistical results of meridian tropism rank from high to low as spleen meridian,liver meridian,lung meridian,heart meridian,stomach meridian,kidney meridian,large intestine meridian,gallbladder meridian,bladder meridian,small intestine meridian,triple energizer meridian and pericardium meridian.There are 18 statistical categories of drug efficacy,and the top five categories are tonic category,heat clearing category,blood circulation promoting and blood stasis removing category,diuresis and dampness eliminating category,and qi regulating category.4.According to the analysis of drug association rules,there are 5 drug patterns and 7 association rules,and there are 4 core drugs: Radix Astragali,Radix Salviae Miltiorrhizae,Poria and Rhizoma Coptidis.Commonly used drug combinations are: Coptis chinensis and Astragalus membranace;Coptidis Rhizoma,Poria;Coptidis Rhizoma,Saviae Miltiorrhizae Radix;Astragalus membranaceus and Poria cocos;Astragalus membranaceus,salvia miltiorrhiza.5.Three groups of drug core combinations were selected by drug cluster analysis: C1: Radix Astragali,Rhizoma Coptidis,Poria,Radix Scutellariae and Radix Salviae Miltiorrhizae;C2: Rhizoma Coptidis,Radix Astragali,Poria,Radix Salviae Miltiorrhizae,Radix Angelicae Sinensis;C3: Rhizoma Coptidis,Poria,Radix Astragali,Radix Salviae Miltiorrhizae,and Atractylodis Rhizoma.6.A total of 91 core drug active ingredients,216 action targets an d 7716 disease targets were obtained by network pharmacological analys is,and 187 targets were intersected by them.The main active ingredien ts are quercetin,kaempferol,luteolin,7-O-methyl-isoslightly convex swo rd Ye Sha alcohol,formononetin,dihydrosalvianolide,salvianolicacid ⅡA,dehydroneocryptosalvianolic acid,4-methyleneosalvianolic acid and carn osic acid.There are 23 key targets,including AKT1,GAPDH,TNF,VE GFA,CASP3 and IL1 B.There are 676 biological function items in GO analysis,involving 625 biological processes,15 cellular components and 36 molecular functions.A total of 105 pathways were obtained by KE GG pathway enrichment analysis,mainly involving AGE-RAGE signal pathway,IL-17 signal pathway,TNF signal pathway and so on.Conclusion:1.Among the 148 cases in this study,male patients are the main ones.In the case data,the most common tongue symptoms are purple tongue and thick white greasy coating,and the most common pulse symptoms are heavy and astringent.In the symptom statistics,abdominal enlargement,dry mouth,fatigue,insomnia,frequent urination,blurred visionand yellow urine are the main symptoms.2.Among the drugs used by the tutor to treat type 2 diabetes mellitus complicated with obesity with phlegm and blood stasis syndrome,the four gases are mainly warm and cold;The five flavors are mainly sweet and bitter,and the meridian tropism belongs to the spleen,liver and lung meridians;The main drugs used are tonifying deficiency,clearing heat,promoting blood circulation and removing blood stasis,diuresis and dampness,and regulating qi.3.The core drugs for the surperviso to treat type 2 diabetes complicated with obesity with phlegm and blood stasis syndrome are Astragalus,Poria,Salvia Miltiorrhiza and Coptidis Rhizoma.Five groups of commonly used drug combinations and three groups of drug core combinations were obtained.4.Through the research of network pharmacology,it is found that the main components of the core drugs are quercetin,kaempferol,luteolin,7-Omethyl-isomicroballoon Ye Sha alcohol,formononetin,dihydrosalvianolide,salvianolide ⅡA,dehydrocryptosalvianolide,4-methylenedi-salvianolic acid,etc.It may act on AKT1,CASP3,VEGFA,RELA,MMP9,TNF,MDM2 and other targets,and play a multi-component,multi-target and multi-channel role in treating type 2 diabetes complicated with obesity by regulating many pathways such as AGE-RAGE signaling pathway,IL-17 signaling pathway and TNF signaling pathway.