Study On The Mechanism And Clinical Observation Of Tangshen Formula In The Treatment Of Diabetic Kidney Disease Based On GEO Differential Gene Analysis And Network Pharmacology

Objective: the first part is to observe the clinical efficacy and safety of Professor Zhang Daning’s "Tangshen prescription" in the treatment of Diabetic Kidney Disease patients with stage Ⅲ ～ Ⅳ by tonifying the kidney and promoting blood circulation,and the second part is to study the pharmacological mechanism of "Tangshen prescription" in the treatment of Diabetic Kidney Disease(DKD)based on GEO differential gene analysis combined with network pharmacology.Through the construction of network pharmacological association between the targets of drug active components and disease differential genes,the mechanism of drug action on disease was discussed.Methods: 1.The clinical observation cases came from outpatients and inpatients in Dingzigu Community Hospital and affiliated Hospital of Tianjin Institute of traditional Chinese Medicine.68 cases met the inclusion criteria,5 cases fell off in treatment,and 63 cases were effective in the end,including 32 cases in the experimental group and 31 cases in the control group.The control group was treated with western medicine,and the experimental group was treated with Tangshen prescription on the basis of symptomatic treatment.The course of treatment was 6 months.The TCM syndrome score,serum creatinine,blood urea nitrogen,estimated glomerular filtration rate,24-hour urinary protein,plasma albumin,glycosylated hemoglobin and liver function of the two groups before and after treatment were compared to determine the curative effect.Finally,SPSS21.0 statistical software was used to analyze the clinical data.2.The drug components of "Tangshen prescription" were searched and supplemented in TCMSP,TCMID and other drug databases and literature.the active components were screened and the molecular targets were predicted according to the properties of ADME(pharmacokinetics).The gene chips related to DKD disease were searched in GEO database for differential gene analysis.The venn diagram was drawn by the intersection of the two,and the drug-disease target network map was constructed.The PPI core protein interaction network was obtained through the STRING online database of the intersecting genes.At the same time,the topological analysis was carried out by Cytoscape3.7.2 software,and the enrichment analysis of GO and KEGG was carried out by R software.Results: part I: 1.Western medicine efficacy evaluation: after 6 months of treatment,the total effective rate of the treatment group and the control group was 78.13% and45.16% respectively.Compared with the two groups,the total effective rate of the treatment group was higher than that of the control group,but there was no statistical difference(P >0.05).2.Comparison of the curative effect of TCM syndrome: after 6months of treatment,the total effective rate of the treatment group and the control group was 90.63% and 71.88%,respectively.The effective rate of the treatment group was better than that of the control group,and the difference was statistically significant(P <0.05).3.Comparison within the group: serum creatinine,glomerular filtration rate and glycosylated hemoglobin were significantly improved in the treatment group(P <0.05),while blood urea nitrogen and glycosylated hemoglobin were significantly improved in the control group(P < 0.05).4.Comparison between groups: there were significant differences in improving the total score of TCM syndrome,serum creatinine and glomerular filtration rate between the treatment group and the control group(P <0.05).The treatment group was better than the control group.Part two: 1.139 kinds of active components and 343 drug targets were selected through database and literature supplement.1046 GEO differential genes were obtained by correcting Pvalue,and 32 related genes were selected after intersection.The biological functions and pathways of related genes were obtained by GO and KEGG enrichment analysis,such as endothelial cell proliferation,regulation,angiogenesis and active regulation of endothelial cell proliferation,extracellular matrix,vesicle cavity,cytoplasmic vesicle cavity and other cellular components containing collagen.Steroid receptor activity,serine hydrolase activity,retinol dehydrogenase activity and other molecular functions,fluid shear stress and atherosclerosis,AGE-RAGE signal transduction pathway and HIF-1signal transduction pathway in diabetic complications.Conclusion: 1.On the basis of the basic treatment of western medicine,the clinical effect of Tangshen prescription in the treatment of stage Ⅲ-Ⅳ DKD is better than that of western medicine alone,which can further improve the serum creatinine and glomerular filtration rate and delay the progress of DKD.2.The main mechanisms of Tangshen prescription in treating DKD are anti-inflammation,hypoglycemia,inhibition of oxidative stress,inhibition of renal fibrosis and so on,it provides a theoretical basis for clinical research.