Study On The Prescription Rule And Core Prescription Network Pharmacology Of Professor Li Mingquan In The Treatment Of Diabetic Kidney Disease

Objective: Using traditional Chinese medicine inheritance assistant system(V2.5)to explore the prescription rule and core prescription of Professor Li Mingquan in the treatment of diabetic nephropathy proteinuria,and predict the possible mechanism of core drugs in the treatment of diabetic nephropathy through network pharmacology.Methods: The first diagnosis data of all patients with diabetic nephropathy treated by Professor Li Mingquan from January 2013 to December 2019 were collected,including general information,symptoms,tongue coating and pulse,auxiliary examination,TCM diagnosis,western medicine diagnosis and complete prescription information.The data were derived from the HIS system of the Information Department of the affiliated Hospital of Chengdu University of traditional Chinese Medicine.After comprehensive manual screening,the relevant data of patients with elevated serum creatinine were excluded,and a total of 295 cases of diabetic nephropathy were included after systematic treatment.The general information of patients,symptoms,pulse condition of tongue coating and complete prescription of traditional Chinese medicine were entered into the inheritance assistant system of traditional Chinese medicine(V2.5).The statistical report module of the system was used to analyze the gender,age,symptoms,tongue coating pulse,four qi and five flavors and menstruation,drug frequency and so on.The improved mutual information method and complex system entropy clustering method in the data analysis of the system are used to mine and analyze the prescription rule,core prescription,new prescription combination and so on.The traditional Chinese medicine system pharmacology database and analysis platform(TCMSP),China knowledge Network and Pub Med are used to search the chemical components and action targets of the core prescriptions,and with the help of the Uni Prot database to query the target genes corresponding to the target genes,the drug target database is established,and combined with the TTD and OMIM databases associated with disease genes,the known action targets of diabetic nephropathy are retrieved,and the potential action targets of diabetic nephropathy are found.Establish diabetic nephropathy target database,and then use Cytoscape(3.7.0)to construct protein interaction network and network analysis,through DAVID into the database for GO enrichment analysis,to predict the possible mechanism of core drugs in the treatment of diabetic nephropathy.Results:The ratio of male to female was about 1.3,and the age was distributed between 31 and 82 years old.The symptoms with high frequency were fatigue,excessive nocturnal urination,dry mouth,low back pain,poor sleep,foamy urine,lumbar acid distension,easy to catch a cold,edema of lower extremities,etc.The tongue was mainly dark red,light red and red,and the tongue coating was yellow,thin and white,and the pulse was thin,slippery,slippery and slippery.According to the statistics of the frequency of traditional Chinese medicine,there were 188 traditional Chinese medicines,The high-frequency sub-drugs mainly include Radix Astragali,Radix Scutellariae,stir-fried Malt,Golden cherry,Cicada slough,Leech,Angelica sinensis,Coptis chinensis,Poria,Euryale seed,Radix Glehniae,Coix seed,Stiff silkworm,Chicken blood vine,Achyranthes bidentata,etc.the four qi were mainly cold,warm and flat,with roughly the same frequency;the five flavors were sweet,bitter,pungent,sour,salty and astringent in order from high to low.Statistics of drug meridian frequency from high to low mainly include liver meridian,spleen meridian,lung meridian,stomach meridian,kidney meridian,heart meridian,large intestine meridian and so on.The rule of association was used to analyze the law of the prescription,and the most frequent combinations were Radix Scutellariae and Radix Astragali,Radix Astragali and Golden Cherry,Radix Astragali and stir-fried Malt,Leech and Radix Astragal,Radix Astragal and Cicada slough.Based on the unsupervised entropy clustering analysis,the four new combinations were 1 bamboo ru,Pinellia ternata,Tangerine peel,Licorice,Fructus Aurantii,Bupleurum and Prunella vulgaris;2 Ginseng,Achyranthes bidentata,Scorpion,Schisandra;3 Raw Rehmannia,Golden cherry,Euryale,Cicada slough,Stiff silkworm,Dilong;4 Pueraria,Polyporus umbellatus,Abdominal skin,Motherwort.The core prescription was composed of the top 10 drugs with high frequency including: Radix Astragali,Radix Scutellariae,stir-fried Malt,Golden cherry,Cicada slough,Leech,Angelica sinensis,Coptis chinensis,Poria,Euryale seed.Through searching TCMSP database,there were 13 active components and 71 potential targets of Radix Astragali,19 active components and 70 potential targets of Radix Scutellariae,15 active components and 57 potential targets of stir-fried Malt,6 active components and 119 potential targets of Golden cherry,2 active components and 67 potential targets of Angelica sinensis,8 active components and 57 potential targets of Coptis chinensis,13 active components and 35 potential targets of Poria,2 active components and 17 potential targets of Euryale seed.including 78 repetitive compound molecules and 160 potential targets.38 potential targets for leeches,24 potential targets for cicadas and 211 potential targets for core drugs were obtained through the search of China knowledge Network and Pub Med.69 targets of diabetic nephropathy were found in TTD and OMIM database.After enrichment analysis,the active components of the core prescription were closely related to 40 target genes involved in diabetic nephropathy,such as EGFR,MAPK1,GRB2,TGFB1,NFKB1,RELA,AKT1,CHUK,IKBKB,PRKCA,TP53,EP300,CDK2,CREBBP,IKBKG and STAT3,mainly involving five signal pathways: HIF-1,Fox O,PI3K-Akt,MAPK and chemokine.Conclusion: According to the data mining results of the inheritance assistant system of traditional Chinese medicine,when Professor Li Mingquan treats diabetic nephropathy proteinuria,he mainly focuses on tonifying deficiency and astringency,eliminating diarrhea and dredging collaterals,supplemented by invigorating spleen,clearing heat and removing dampness,etc.that is,sweet and warm drugs such as Radix Astragali and Angelica sinensis(tonifying deficiency)are mainly used to tonify qi and blood,Cicada slough,Leeches and other insect drugs to achieve the effect of removing blood stasis and dredging collaterals.At the same time,they are combined with Scutellaria baicalensis and Coptis chinensis to clear away heat and dehumidi.Poria and stir-fried Malt to strengthen the spleen.Its core prescriptions are Radix Astragali,Radix Scutellariae,stir-fried Malt,Golden cherry,Cicada slough,Leech,Angelica sinensis,Coptis chinensis,Poria,Euryale seed,reflecting Professor Li Mingquan's important idea in the diagnosis and treatment of diabetic nephropathy proteinuria.Through the establishment of component-target-disease interaction network,the active components of the core prescription are related to multi-targets and multi-pathways.Among them,EGFR,MAPK1,GRB2,TGFB1,NFKB1,RELA,AKT1,CHUK,IKBKB,PRKCA,TP53,EP300,CDK2,CREBBP,IKBKG,STAT3 and other targets are closely related to the core prescription and diabetic nephropathy.The core prescription may play a therapeutic role in diabetic nephropathy through HIF-1,Fox O,PI3K-Akt,MAPK and chemokine signaling pathways,which are mainly involved in oxidation,inflammation,metabolism,renal fibrosis,cell proliferation and apoptosis regulation and other biological pathways to protect the kidney.