| Objective:1.To collect TCM compounds used by various doctors in the treatment of diabetic kidney disease in the past 20 years,and to comprehensively analyze the medication rules and core drugs of TCM in the treatment of diabetic kidney disease by using data mining technology,so as to provide new ideas for the treatment of diabetic kidney disease.2.Through the results obtained by data mining,the effective components,targets,pathways and mechanism of the treatment of diabetic kidney disease with spleen-kidney deficiency,dampness and turbid blood stasis by Baoshen mixture were further explored.Methods:1.Based on CNKI,VIP,Wanfang database,the relevant clinical efficacy observation literature of traditional Chinese medicine in the treatment of diabetic kidney disease was collected,and a literature database was created to statistically analyze the symptom type of diabetic kidney disease,the drug frequency,efficacy,four qi,five flavors,meridian tropism,association rules,and entropy clustering,and explore the medication rules and core drugs of traditional Chinese medicine in the treatment of diabetic kidney disease,and excavate potential new formulas.2.Combined with the common etiology and pathogenesis of diabetic kidney disease,TCM syndrome type,clinical medication experience and data mining results,Baoshen mixture was determined as the object to explore its mechanism in the treatment of diabetic nephropathy with spleen and kidney deficiency and dampness and turbid blood stasis..3.All the chemical components and targets of Baoshen mixture were retrieved through TCMSP database and Huayuan databases,the targets of diabetic kidney disease were predicted through UniProt and GeneCards databases,and the common targets of disease and drug components were obtained by Venny software.The common targets were introduced into Cytoscape3.7.1 software to construct the compound-target network diagram,and the protein interaction network of them was constructed in the STRING database to screen the core protein genes.GO function enrichment analysis and KEGG metabolic pathway enrichment analysis were carried out by Metascape for the core targets of Baoshen mixture in treating diabetic kidney disease with spleen-kidney deficiency,dampness and turbid blood stasis.And the core active components were docked with key targets using molecular docking technology.Results:1.In this study,a total of 107 related clinical literatures were collected,in which there were more males than females,and the age of onset was mainly distributed between 50 and 59 years old.The top five TCM types are deficiency of both qi and yin,deficiency of both yin and yang,qi deficiency of spleen and kidney,yin deficiency and dryness heat,yang deficiency of spleen and kidney.A total of 153 kinds of drugs were involved,with a frequency of 1185,and 35 medicines were used more than 10 times,and the top 3 categories of traditional Chinese medicine were deficiency-tonifying drugs,blood-activating and blood-stasis-promoting drugs,and diuresis and dampness-promoting drugs.In the statistics of "four qi",warm and cold were the main characteristics;in the statistics of "five tastes",sweet and bitter were the main characteristics;in the statistics of meridian tropism,kidney,spleen and liver were the main characteristics.The core drugs are Radix astragali,Poria cocos,Atractylodes macrocephala,Codonopsis pilosula,Angelica sinensis,Rhubarb,Achyranthes bidentata,Radix paeoniae alba,etc.Through entropy cluster analysis method,18 core combinations and 9 new formulas are obtained.2.The network pharmacological results showed that there were 121 effective compounds of Baoshen mixture,566 predicted target were collected after removing repetition,1299 genes related to "Diabetic kidney disease" were searched,and 211 common targets between them.The top 10 core targets included SRC,STAT3,PIK3R1,MAPK3,MAPK1,PIK3CA,RELA,TP53,HSP90AA1,and AKT1.The key drug ingredients in Baoshen mixture for the treatment of diabetic kidney disease include quercetin,kaempferol,leucine and palmitoleic acid.The enrichment results of KEGG pathway showed that Baoshen mixture could play a therapeutic role by regulating PI3K-Akt signaling pathway,JAK-STAT signaling pathway,Adipocutokine signaling pathway,GnRH signaling pathway,Wnt signaling pathway,Diabetic cardiomyopathy,Pathways in cancer,Proteoglycans in cancer,Chemical carcinogensisreceptor activation and so on.3.The results of molecular docking showed that the binding energies of the core drug components including quercetin,kaempferol and leucine with key targets including SRC,STAT3 and PIK3R1 were all less than-5,this shows that there is a well combination between them.Conclusion:1.In the traditional Chinese medicine treatment of diabetic kidney disease is based on the deficiency of spleen and kidney,with dampness,turbidity,blood stasis and poison.The main effects of the drugs are tonifying spleen and kidney,promoting diuresis and dampness,promoting blood circulation and removing blood stasis,replenishing qi and nourishing yin.And the drugs can be added or reduced according to the clinical symptoms of the patients,such as patients with yang deficiency of spleen and kidney can use drugs for warming spleen and kidney,nourishing yang and promoting diuresis;patients with qi deficiency and blood stasis can use drugs for invigorating spleen and kidney,activating blood circulation and removing blood stasis;patients with deficiency of spleen and kidney yin can use drugs for nourishing yin,clearing dampness,removing blood stasis and detoxification;patients with deficiency of liver and kidney can use drugs for tonifying qi and nourishing yin and tonifying liver and kidney.2.Baoshen mixture mainly regulates the targets of SRC,STAT3,PIK3R1,MAPK3,MAPK1,PIK3CA,RELA,TP53,HSP90AA1,AKT1,and regulates PI3K-Akt signal pathway,JAK-STAT signal pathway,Wnt signal pathway and GnRH signal pathway to exert its therapeutic effect on diabetic kidney disease with spleen and kidney deficiency,dampness and turbid blood stasis. |
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