| Objective: Diabetic Kidney Disease(DKD)is the most serious complication of diabetes,a serious threat to the lives of diabetics,to the patient’s family and society caused a great burden.In recent years,a large number of literature have reported that traditional Chinese medicine has protective effect on renal function of diabetics,and can delay the process of DKD,improve the quality of patients’ life.Through clinical observation before,modified Shenshuning prescription has played a good effect in the treatment of qi-yin deficiency DKD patients,can improve the symptoms of patients,delay the development of the disease.On this basis,this study conducted further research and statistics on the clinical efficacy of modified Shenshuning prescription,and analyzed its possible mechanism and action targets through network pharmacology,in order to provide scientific basis for clinical application and experimental design.Method: The first part:Through TCMSP database,the active components and targets of 10 traditional Chinese medicines in “ modified Shenshuning Prescription ” were screened.Uni Prot database was used to screen out the human targets of drugs and to correct them.The potential targets of the disease were obtained by searching "Diabetic Nephropathy" in OMIM、Genecards and Drugbank database.The drug targets and the potential targets of the disease were matched to screen out the drug-disease associated target genes.Cytoscape software was used to construct the gene network diagram of the active components and targets for analysis.The proteins interaction network map was constructed by using the STRING online database.Go and KEGG enrichment analysis of associated target genes was performed by using Metascape online database.Part II: Patients diagnosed with Qi-Yin deficiency DKD in the Nephrology Department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2019 to December 2020 were selected.According to the criteria of rejection,100 cases were screened and retrospectively studied.Modified Shenshuning Prescription was used for 3 months as a cycle and observed for 1 cycle.The scores of TCM symptoms and related laboratory indexes(24-hour urinary protein,microalbuminuria,total microalbuminuria,urinary acetylglucosidase,glycosylated hemoglobin,high-density lipoprotein,low-density lipoprotein,triglyceride,cholesterol,serum creatinine,urea nitrogen,glomerular filtration rate,alanine aminotransferase,etc.)The data were analyzed by SPSS 22.0.Adverse reactions were recorded and clinical effects were analyzed.Result:The first part: In TCMSP database,a total of 149 active components and 250 protein targets were obtained after screening 10 TCM in “modified Shenshuning Prescription”,998 potential disease targets were obtained in the database,and 105 associated targets were obtained by intersection of disease targets and drug targets.The active component target network was constructed based on Cytoscape software,and the active components with high correlation were identified as quercetin,kaempferol,luteolin,7-o-methyl isoeugenol,wogonin,formononetin,isorhamnetin,β-sitosterol,etc.;the main associated genes obtained by PPI network analysis were AKT1、IL6、TNF、MAPK8、TP53、VEGFA、MAPK1、JUN、EGF、IL1B et al.The enrichment results of GO analysis were mainly related to cell response to growth factors,response to extracellular stimulation,regulation of DNA binding transcription factor activity,leukocyte differentiation,active regulation of cell death,active oxygen metabolism and other biological processes;KEGG pathway enrichment showed that gene targets were significantly enriched in cancer signaling pathway and AGE-RAGE signaling pathway in diabetic complications In addition,they are also involved in relaxin signaling pathway,insulin resistance pathway and NF-KB pathway.The second part: After 1 cycle(3 months)of treatment,the total effective rate was 77%,and the difference was statistically significant(P < 0.05).The total effective rate of TCM syndrome was 81%,and the difference was statistically significant(P < 0.05).The main symptoms were soreness and weakness of waist and knee,fatigue,limb edema,shortness of breath and lazy speech.After taking drugs,the clinical symptom scores and total scores were lower than before,with statistical difference(P < 0.05).24-hour urinary protein,microalbuminuria,total microalbuminuria,urinary acetylglucosidase,glycosylated hemoglobin,low density lipoprotein,triglyceride,cholesterol,serum creatinine and urea nitrogen were significantly lower than before(P < 0.05).Glomerular filtration rate increased after treatment,the difference was statistically significant(P < 0.05).There was no significant difference in ALT,AST,co2 cp,K,CL before and after treatment(P > 0.05).There were no adverse reactions,dizziness,headache,vomiting,stool changes,allergic reactions,irregular menstruation and other symptoms.Conclusion: 1 Shenshuning Modified Prescription can improve the quality of life of DKD patients with deficiency of both qi and yin,and no serious adverse reactions have been found in clinical observation,indicating that it has a certain degree of safety.2 Shen Shu Ning Jiajian Decoction has a protective effect on the renal function of DKD patients with deficiency of both qi and yin.It can regulate blood lipid levels and improve the 24-hour urine protein quantitative level.3 Based on network pharmacology to analyze the possible mechanism of Shenshuning Modified Recipe in the treatment of diabetic nephropathy,it is believed that its core active ingredients include quercetin,kaempferol,isorhamnetin,formononetin,wogonin,etc.By mediating the AGE-RAGE signaling pathway,relaxin signaling pathway,insulin resistance pathway,NF-к B signaling pathway,sphingolipid signaling pathway,JAK-STAT signaling pathway,it has a therapeutic effect on DKD. |
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