Based On Data Mining And Network Pharmacology To Explore Professor Yang Yulan’s Clinical Experience And Mechanism Of Action In The Treatment Of Diabetic Kidney Disease

Objective:Diabetic nephropathy(DKD)is the most common microvascular disease of diabetes mellitus,which is caused by abnormal metabolism of diabetes mellitus.With the improvement of our living standard,the aging of the population and other factors,the incidence of diabetic nephropathy has gradually increased.Traditional Chinese medicine has many therapeutic targets,which can not only nourish Qi and nourish Yin,promote blood circulation and clear collaterals,improve symptoms,but also regulate Yin and Yang and regulate immune function,showing unique advantages in the treatment of DKD.Professor Yang Yulan has been engaged in clinical work for more than 30 years.She has excellent medical skills and profound knowledge.She has unique insights and rich experience in the treatment of chronic kidney disease,and has achieved significant clinical efficacy.Moreover,network pharmacology is used to predict the target and pathway of core drug action DKD,so as to contribute to the inheritance and innovation of TCM.Method:1.Medical records of all patients with DKD diagnosis received by Professor Yang Yulan from September 2018 to September 2020 were collected,mainly including general information,symptoms,tongue pulse,auxiliary examination,TCM prescription,TCM and Western medicine diagnosis,etc.A total of 111 cases that met the requirements of this study were screened.SPSS 25.0 and SPSS Modeler18.0 was used for data analysis to summarize the rules,and the core drugs and prescription rules of Professor Yang Yulan in the treatment of DKD were discussed.2.Use TCMSP database,Batman-TCM database,CNKI,Pub Med and other databases to search the effective chemical components and action targets of core prescriptions,and use Uniprot database to query the gene proteins corresponding to targets to establish drug target database,combined with Gene Cards database associated with disease genes.The known action targets of diabetic nephropathy were retrieved to find out the potential action targets of diabetic nephropathy,and the drug-diabetic nephropathy target database was established.The drug-target-disease protein interaction network was constructed by Cytoscape(3.7.0),and the potential target protein interaction network was obtained by using the String database.Go functional annotation and KEGG pathway enrichment analysis of target genes were performed using Bioconductor package and R language to predict the possible mechanism of action of core drugs in the treatment of diabetic nephropathy.Results1.Gender and age distribution: A total of 111 patients were included,of which the male to female ratio was about 1.22:1.Age distribution ranged from 29 to 84,with 81(73.0%)aged from 50 to 702.Frequency of Drugs,Four Qi and Five Flavor,and Rehmannia sinensis Results: There were 527 prescriptions.According to the frequency statistics of traditional Chinese medicine,there were 252 kinds of traditional Chinese medicine in total.The four qi are mainly cold,warm and flat,and the frequency of cold and warm is roughly the same.The frequency of five flavors was bitter,followed by sweet,spicy,salty,astringent,sour and light.According to the statistics,the drug meridians were liver,lung,stomach,spleen,kidney,heart,large intestine,bladder,gallbladder,small intestine,pericardium,and three Jiao meridians in turn.3.Drug association rule relationship and high-frequency drug system cluster analysis:The association rule was used to analyze the formula rules,and 18 second-order association rules were obtained,such as astragalus + chuanxiong,salvia miltiorrhiza + chuanxiong,astragalus + salvia miltiorrhiza,etc.There are 19 association rules of third order and above,such as Astragalus + Ligusticum chuanxiong + Salvia miltiorrhiza,Astragalus + Pueraria +Salvia miltiorrhiza,Astragalus + dogwood + Ligusticum chuanxiong,etc.Five groups were clustered by systematic clustering method.The first group was Rhubarb charcoal,Puhuang charcoal,Safflower,Rhubarb,Salvia miltiorrhiza,Alisma radix,Epimedium,Ligusticum chuanxiong,Astragalus membranaceus,Cornus officinalis,Chinese herb,Perilla leaves,Platycodon grandiflorum,dried ginger,corduum seed,Trichosanthis trichosanthis,Fructus aurantii,Root of chicken.The second group for the cherry,Gordon euryale seed,green wind vine,shepherd’s shepherd’s bag,angelica,silkworm sand,rhodiola rosea,bupleurum,scutellaria,poria cocos,ground dragon,Hedyotis diffusa,the third group for the mulberry leaf,Coptis chinensis,raw rehmannia,Radix Sophora root,Flos Lonicerae,Flos Lonicerae,Flos Lonicerae,Flos Lonicerae,Chinese yam,Phellodendron chinensis,the fourth group for jujube seed,polygon,oyster,The fifth group was notoginseng,wolfberry fruit,caulis spatholobi,gastrodia elata,pueraria root,gu shemu,luxiaocao,mulberry parasitic fungus,eucommia ulmoides,oxutanthus cassia,sappanwood,papaya,tangerine,leech.According to the association rules,the final core prescription was Astragalus membranus,Ligusticum chuangusticum,Salvia miltiorrhiza,Radix Puerariae,Digitalgia officinalis,Cornus officinalis,Rhizoma coptis,Angelica sinensis,Rehmannia glutinosa and Red Safflower,namely the composition of the top 10 drugs in drug use frequency.4.Network pharmacological analysis results: the core prescription was composed of the top 10 drugs with high frequency of use,mainly including Astragalus membranus,Ligusticum chuanxiong,Salvia miltiorrhiza,Radix Puerariae,Digitalgia officinalis,Cornus officinalis,Rhizoma coptidis,Angelica sinensis,Rehmannia glutinosa and Safflower.The core drugs actually contain 100 effective chemical components,such as quercetin,stigmasterol,formononetin,etc.,and 333 drug action targets in total.A total of 545 targets related to diabetic nephropathy were screened,and a total of 78 intersecting targets were found between10 drugs and the disease,such as PTGS2,NOS2,ESR1,AR,PPARG,etc.Enrichment analysis of GO and KEGG pathways revealed 152 signaling pathways that may be related to the treatment of DKD by this prescription.This is most likely through the AGE-RAGE signaling pathway in diabetic complications,Fluid shear stress and atherosclerosis Atherosclerosis,TNF signaling pathway,IL-17 signaling pathway and other signaling pathways have a protective effect on the kidney.Conclusion:according to the result of data mining,yu-lan Yang,a professor at the treatment of diabetic nephropathy,more is given priority to with relatively weak,heat of blood,accompanied by spleen dehumidification detumescence,etc.,which is given priority to with astragalus root,angelica to make up for qi and blood,rhizoma ligustici wallichii,salvia miltiorrhiza,and safflower in the effect of promoting blood circulation to remove blood stasis,eliminating t2 dm,at the same time as the compatibility of radix rehmanniae,rhizoma coptidis and other medicine carambola dehumidification,nourishing Yin,puerarin in muscle antifebrile,sun Microsystems fluid.The core prescriptions are ten medicines of Astragalus membranus,Ligusticum chuanxiong,Salviae miltiorrhiza,Radix Puerariae,Dogwood officinalis,Rhizoma Rhizoma,Angelica sinensis,Rehmannia glutinosa and Safflower,which reflects the important thinking of Professor Yang Yulan in the diagnosis and treatment of DKD.The core prescription active ingredient is associated with multiple targets and multiple pathways through the interaction network relationship between component,target and disease.The core prescription drug may be through the AGE-RAGE signaling pathway in diabetic complications,Fluid shear stress and atherosclerosis,tumor necrosis factor signaling pathway,and interleukin-17 signaling pathway Pathway)and other signaling pathways,which are mainly involved in the regulation of cell proliferation and apoptosis,inflammatory response,oxidative stress response,renal fibrosis and other pathways.