Research On The Medication Rule And Mechanism Of Professor Zhang Zongli Treating Chronic Glomerulonephritis Based On Data Mining And Network Pharmacology

Objective:To summarize Professor Zhang Zongli’s medication rule and academic experience in treating chronic glomerulonephritis(CGN)relying on traditional Chinese medicine inheritance system(TCMIS)(V2.5);and retrieve key drug combinations’ active ingredients,then probe their mechanisms of action in treating different syndrome types of CGN primarily drawing support from network pharmacology.Methods:1 The records of outpatients with CGN in Professor Zhang Zongli’s clinic from January2018 to October 2019 in Affiliated Hospital of Tianjin Academy of Traditional Chinese Medicine were collected.Excel software was used to count patients’ general conditions.Then analysed the medication rule of Professor Zhang in treating CGN by Apriori algorithm and entropy clustering algorithm in TCMIS.2 Key drug combinations’ active ingredients and their gene targets of different syndromes of CGN from TCMSP and CGN related targets were screened,then took the intersection.The relationship of network between ingredients and taegets was shown by Cytoscape3.2.1.The intersected genes’ protein protein interaction network was analyzed by STRING website,and screened the key targets by Cyto NCA.The key targets’ GO terms and KEGG terms were analyzed by DAVID,then were shown by Omic Share Tools.Results:1 This study contained 148 cases of clinical records,517 department visits and 517 prescriptions.The number of male patients was 67 and female patients was 81,their ages ranged from 21 to 75.Syndrome types frequency analysis results: the mixed syndrome of excess and deficiency was 442;the most common syndrome type was spleen and kidney Qi deficiency and damp-heat syndrome and the second was hepatic and renal Yin deficiency and damp-heat syndrome.176 prescriptions of spleen and kidney Qi deficiency and damp-heat syndrome type included 116 kinds of traditional Chinese medicine.116 herbal medicines properties statistics: cold property and sweet herbal medicine frequency of drug used the most;channel tropism statistics: the herbal medicines which pass through spleenchannel were the majority.According to the drug efficacy,116 herbal medicines were divided into 15 categories,diuretics for eliminating dampness herds had the highest frequency,then tonify deficiency and heat medicines.16 kinds herbal medicines in the 176 prescriptions were used more than 50 times.Association rule analysis results: there were 28 high-frequency drug combinations and 29 association rule terms.At the condition of “the number of support= 100,confidence = 0.9”,key drug combination:Huangqi-Fuling-Danggui-Cheqiancao was obtained.Entropy clustering analysis results: 16 drug combinations and 8 new prescriptions were obtained.130 prescriptions of hepatic and renal Yin deficiency and damp-heat syndrome type included 134 kinds of traditional Chinese medicine.134 herbal medicines properties statistics: the top of four natures and five flavours of drugs frequency was cold property and sweet;channel tropism statistics: the herbal medicines which pass through liver channel were the majority.According to the drug efficacy,134 herbal medicines were divided into 17 categories.That the highest frequency herds were used were deficiency-nourishing drugs,the folloed were diuretics for eliminating dampness and antipyretic drugs.24 kinds herbal medicines in the 230 prescriptions were used more than 20 times.Association rule analysis results: there were 65 high-frequency drug combinations and 33 association rule terms.At the condition of “the number of support = 52,confidence = 0.9”,key drug combination: Nuzhenzi-Hanliancao-Cheqiancao,Jinyinhua-Danzhuye was obtained.Entropy clustering analysis results: 18 drug combinations and 9 new prescriptions were obtained.2 441 CGN related gene targets were retrieved.Key drug combination of spleen and kidney Qi deficiency and damp-heat syndrome contained 30 active ingredients and 230 gene targets.Their intersected gene targets were 58.AKT1 、VEGFA and IL6 and so on were the core targets.According to the gene analysis,115 GO terms(p<0.05)which included 87 biological process terms,10 cellular composition terms and 18 molecular function terms,and 98 KEGG pathways were obtained(p<0.05).Key drug combination of hepatic and renal Yin deficiency and damp-heat syndrome contained 38 active ingredients and 239 gene targets which have 57 common genes with CGN.AKT1 、 VEGFA and EGFR and so on were the core targets.According to the gene analysis,115 GO terms(p<0.05)which included 84 biological process terms,9 cellular composition terms and 22 molecular function terms,and 90 KEGG pathways were obtained(p<0.05).Conclusion:1 Professor Zhang Zongli’s medication rule and academic ideology can be summarized by the high-level data mining method.What’s more,it provides reliable basis for Professor Zhang’ experience inheritance and clinical treatment of CGN.2 The study of mechanisms of key drug combinations in treating CGN fully embodies the traditional Chinese medicine’s characteristics of multi-component,multi-target and multi-channel action,provides a reference for profound study.There are the same chemical components,gene targets and signaling pathways in different syndromes,and differences,too.This demonstrates traditional Chinese Medicine’s connotation of treating the same disease with disease with different methods.