Professor Song Liqun’s Discussion On The Law Of Drug Use And Network Pharmacology Mechanism In The Treatment Of Chronic Renal Failure

ObjectiveThis paper summarized professor Song Liqun’s clinical experience in differentiation and treatment of chronic renal failure,explored the medication rules and prescription characteristics of differentiation and treatment of chronic renal failure,and explored the mechanism of network pharmacology among different syndrome types.Methods1.This paper summarizes professor Song Liqun’s clinical experience and academic viewpoint on the treatment of chronic renal failure by sorting out the cases of clinical diagnosis and treatment of chronic renal failure.2.According to inclusion and exclusion criteria,a total of 97 9 patients with chronic renal failure who were treated by Professor Song Liqun in the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from January 2011 to September 2021 were collected.The included cases were standardized,classified and uploaded to the traditional Chinese Medicine Inheritance computing Platform(V3.0)according to the TCM syndrome diagnosis criteria,and data analysis,association rules,clustering analysis and other functional modules were used for data mining to analyze the drug use characteristics of different TCM syndromes.To summarize professor Song Liqun’s law of drug use and the relationship between core drug combination and syndrome differentiation and treatment differentiation of chronic renal failure.3.According to the clinical experience of differentiation and treatment of chronic renal failure by our tutor and the analysis of data mining of included cases,it is concluded that the common TCM syndromes of differentiation and treatment of chronic renal failure by Professor Song Liqun include spleen-kidney qi deficiency syndrome,blood-stasis syndrome and water-dampness syndrome,and they are named as "Spleen-invigorating kidney Prescription","Promoting blood stasis prescription" and "invigorating dampness Prescription"respectively.Network pharmacology and molecular docking technology were used for analysis,and TCMSP database was used to retrieve and obtain the chemical components and potential action targets of core prescription drugs,and their action relationships were displayed through Cytoscape 3.8.0.Screening of chronic renal failure disease targets from GeneCards,OMIM,PharmGKB,Drugbank and TTD databases;After extracting the intersection targets of drugs and diseases,it was imported into STRING database for protein interaction network analysis and PPI network construction.Cytoscape software was used to screen core genes.GO and KEGG gene function and pathway enrichment were analyzed by R language.AutoDock Vina was used for molecular docking of drug active ingredients and core target proteins.Results1.Distribution of basic diseases:Through the statistics of basic diseases of all the included cases,the results showed that secondary kidney diseases accounted for the majority of the patients,with hypertensive nephropathy being the most,up to 612 cases,accounting for 62.51%;Diabetic nephropathy was followed by 206 cases(21.04%).152 cases(15.53%)had hyperuric acid renal damage.82 cases of chronic glomerulonephritis(8.38%)were primary renal diseases.4 5 cases of nephrotic syndrome(4.60%);36 cases(3.68%)had polycystic kidney disease.2.Statistical results of TCM syndrome type:among 979 cases of chronic renal failure,7 62 cases of spleen-kidney qi deficiency,accounting for 77.83%;There were 286 cases of blood stasis syndrome(29.21%).Water-dampness syndrome 27 6 cases(28.19%);117 cases of liver and kidney Yin deficiency syndrome,accounting for 11.95%;92 cases were damp-heat syndrome,accounting for 9.40%;There were 84 cases of poisoning by drowning(8.58%).52 cases of qi and Yin deficiency syndrome,accounting for 5.31%;29 cases of spleen and kidney Yang deficiency,accounting for 2.96%;Deficiency of Yin and Yang syndrome 19,accounting for 1.94%.3.Symptom statistical results:Symptom frequency from high to low in 97 9 cases of chronic renal failure were as follows:Fatigue(57.51%),lumbago(5 1.99%),facial edema(33.30%),dizziness(3 1.15%),turbidness(21.04%),nocturnal frequent urination(20.43%),long urination(19.71%),lack of appetite(19.00%),palpitation(11.95%),dry stool(10.21%))etc.4.Drug statistical results:In 979 first prescriptions,the frequency of four gases used was warm,flat,cold,cold and hot from high to low.The frequency of five tastes was sweet,bitter,spicy,sour and salty from high to low.The frequency of meridian of drugs used from high to low was spleen,liver,stomach,kidney,lung,large intestine,heart,gallbladder,pericardium,bladder,small intestine and tricoke meridian.The top 10 drugs in the list of drug use frequency were Atractylodes atractylodis,astragalus membranaceus,rhubarb,Apocynum venetum leaf,Herba catulata,Centella asiatica,eucommia charcoal,dandelion,euryferox seed and cherry cherry.5.Based on association rules analysis,will support the number is set to 600 degrees,the confidence level is set to 1,it is concluded that professor li-qun song core drug combination for the treatment of chronic renal failure:astragalus,atractylodes,rhubarb,apocynum leaves,eucommia bark carbon extract,centella asiatica extract,cat grass,dandelion.6.According to drug frequency,association rules and cluster analysis,the medication rules of chronic renal failure of common TCM syndromes were obtained:6.1The core drug combination of chronic renal failure syndrome of spleen-kidney qi deficiency was:Atractylodes atractylodis,astragalus membranaceus,Poria coxburghii,eururox seed,fructus lucidi,liquorice,Fructus ligustri,tangerine peel,raspberry and Yam;6.2The core drug combinations of chronic renal failure and blood stasis syndrome are atractylodes macrocephala,Astragalus membranaceus,Rhubarb,salvia miltiorrhiza,turmeric,caulis spatholobus and turmeric;6.3The core drug combinations of chronic renal failure water-dampness syndrome were atractylodes macrocephala,Astragalus membranaceus,Poria cocos,Centella asiatica,Apocynum venetum leaf,Mulberry white bark,Lulutong and Fenlu.7.Based on association rule analysis,the commonly used drug combinations were:Astragalus membranaceus and Atractylodes atractylodes,Bupleurum,paeoniae paeoniae and Immaturus aurantii,Centella asiatica,Herba catechifolia and elion,turmeric and turmeric,Mulberry white bark,Lulutong,fenlu lu and loofah.8.Network pharmacology Drug action Pathway research Results:8.1 Enrichment analysis of KEGG pathway of Spleen-invigorating and Kiden-nourishing prescription,the main enrichment pathways were PI3 K-Akt signaling pathway,age-rage signaling pathway,IL-17 signaling pathway,TNF signaling pathway,HIF-1 signaling pathway,etc.8.2Enrichment analysis of KEGG pathway of Huoxue Quyu Recipe,the main enrichment pathways were PI3K-Akt signaling pathway,age-rage signaling pathway,IL-17 signaling pathway,TNF signaling pathway,etc.8.3Enrichment analysis of KEGG pathway in the moisture-enhancing prescription,the main enrichment pathways were PI3 K-Akt signaling pathway,MAPK signaling pathway,age-rage pathway,IL-17 signaling pathway,TNF signaling pathway,HIF-1 signaling pathway,etc.9.Results of docking study on drug active ingredients in network pharmacology:9.1 The active ingredients of spleen-invigorating and kidney-invigorating prescription may be quercetin,luteolin,diosgenin,glycyrrhizin A and β-carotene,which are mainly related to the regulation of AKT1,JUN,CCND1 and RB1 genes.It may delay the progression of disease by affecting the growth,metabolism,proliferation,differentiation and apoptosis of cells and other biological processes.9.2The active ingredients of huoxue Quyu Prescription may be quercetin,luteolin,tanshinone ⅡA,licorice chalcone A,aloe emodin and hidden tanshinone.The effect of huoxue quyu prescription on promoting blood circulation and removing blood stasis is related to the regulation of CCND1,JUN,MAPK14,TP53 and RB1 genes.It may play a role in delaying disease progression by affecting endothelial cell injury repair,platelet aggregation,regulating immune and inflammatory responses.9.3The active ingredients that play a role in treating diseases in the prescription for dampness may be quercetin,luteolin,kaoneferol and formononetin.The effect on dampness is related to the regulation of AKT 1,JUN,MAPK 14 and RB1 genes,and may play a role in delaying disease progression by regulating immunity,inflammatory response and cell cycle.Conclusion1.Professor Song Liqun differentiated the treatment of chron ic renal failure based on the theory of the five zang organs and the theory of gasification.He believed that the key pathogenes is of chronic renal failure was the deficiency of spleen and kid ney and the accumulation of dampness and toxin.The treatment should strengthen spleen and kidney,nourish dampness and rem ove stasis.2.Professor Song Liqun focuses on the treatment of chronic renal failure by both spleen and kidney.In the future,the nat ure is replenishing,and the method of invigorating dampness an d removing stasis is used to soothe sanjiao and restore qi opera tion.Core drug combinations as:astragalus,atractylodes,rhubar b,apocynum leaves,eucommia bark carbon extract,centella asia tica extract,cat grass,dandelion.3.Network pharmacology studies suggest that professor Song Liqun’s core experience prescription for differentiation and trea tment of chronic renal failure including spleen-kidney qi deficie ncy syndrome,blood-stasis syndrome and water-dampness syndro me can all act on signal pathways related to chronic renal failu re:Ages-rage signaling pathway,IL-17 signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway and MAPK signaling pathway play a therapeutic role,w hile there are differences among different syndrome types.Amon g them,The Prescription for Invigorating spleen and Yishen has obvious enrichment in HIF-1 signaling pathway.However,the MAPK signal pathway was enriched significantly by liwei prescr iption.4.Molecular docking studies suggested that although the co mponents of the three drugs were different,their core targets w ere partly the same,and the active ingredients of the three dru gs could act on CCND1,FOS,HIF1A,JUN,MAPK14,MYC,TP 5 3 and RB1.However,there are differences among the three par ties:Spleen-invigorating and kiden-benefiting prescription mostly acts on AKT1,MAPK3 and STAT3;Huoxue Quyu Formula was closely related to EGFR,MAPK3,MDM2 and STAT3.The wet p rescription is more inclined to AKT1 and MDM2.