Clinical Control Study And Network Pharmacology Analysis Of Modified Huangqi-Guizhi-Wuwu Decoction In The Treatment Of Diabetes Nephropathy(Stage Ⅳ-Ⅴ)

Objective:1.To evaluate the efficacy and safety of modified Huangqi-Guizhi-Wuwu Decoction in the treatment of diabetes nephropathy(DN)(stage Ⅳ-Ⅴ).2.Carry out network pharmacological analysis on modified Huangqi-Guizhi-Wuwu Decoction.Explore the potential therapeutic targets of drug therapy for DN,and provide theoretical basis for the treatment of DN with our prescription.Method:1.Study subjects: From February 2022 to December 2022,39 patients with diabetes nephropathy were selected from the Dalian Medical University Affiliated First Hospitall.Subjects were divided into a test group and a control group,and received treatment for 12 weeks.Both groups were given conventional basic treatment,and the experimental group was given additional flavors of Huangqi Gui Zhi Wuwu Tang on top of the basic treatment,100 ml each time,taken orally twice a day.The two groups were treated for 12 weeks.Compare the changes of TCM syndrome score,24-hour urinary protein content,urinary albumin /creatinine,blood lipid and renal function between the two groups.SPSS27.0 software was used to carry out statistical analysis on all data and data,and compare the difference of results within and between groups before and after treatment.2.(1)The active ingredients and disease corresponding targets in the prescription of Modified Huangqi-Guizhi-Wuwu Decoction were searched through Traditional Chinese Medicine Systems Pharmacology and BATMAN databases,and the DN targets were searched through Gene Cards and Online Mendelian Inheritance in Man database.(2)Use Cytascape 3.9.1 to construct the active component-target network of the modified Huangqi-Guizhi-Wuwu Decoction and DN,and screen for its key components in the treatment of DN.(3)PPI network diagram of conformational protein interactions through the STRING database.,and according to the degree value,the core target of modified Huangqi-Guizhi-Wuwu Wuwu Decoction for treating DN was selected(4)Gene ontology(go)and Kyoto Encyclopedia of genes and genomes(KEGG)enrichment analysis were performed on the intersection target to obtain the DN trentment with modified Huangqi-Guizhi-Wuwu Decoction highly specific pathway.Result:1.A total of 39 patients who met the criteria were included in this study.During the trial,6 patients failed to complete the follow-up due to the impact of the epidemic situation and the late enrollment time,and were excluded.Before treatment,there was no statistical difference between the two groups in basic information and test results(P>0.05),which was comparable.(1)Comparison of renal function: After treatment,creatinine and urea in both groups improved compared with those before treatment(P<0.05),and the improvement in the test group was more obvious(P<0.05).(2)24-hour urine protein content and urine microalbumin /creatinine: After treatment,patients in both groups improved(P<0.05),and the improvement in the test group was more obvious(P<0.05).(3)blood lipids: the total cholesterol and triglyceride were better in both groups than before(P<0.05),and the improvement in the test group was more obvious(P<0.05).(4)Blood potassium:After treatment,the blood potassium of patients in the two groups did not change significantly(P>0.05)(5)Liver function: after treatment,the alanine aminotransferase and aspartate aminotransferase in the test group did not change significantly(P>0.05)(6)TCM syndrome score and TCM syndrome efficacy: After treatment,the TCM syndrome score of patients in the two groups decreased slightly(P<0.05);TCM syndrome effect: the effective rate of the test group was 92.30%,and that of the control group was 60%.2.Network pharmacology results:(1)Through database screening and integration,115 potential active ingredients were obtained and 95 overlapping targets were obtained.(2)The network pharmacology method was used to analyze the modified Huangqi-Guizhi-Wuwu Decoction and DN.By ranking the degree values of the compound components in the interactive network,it was concluded that quercetin,kaempferol,luteolin,ursolic acid,etc.might be the key drug components of the modified Huangqi-Guizhi-Wuwu Decoction acting on DN.(3)Through topological analysis,we can know that target protein nodes such as ALB,IL6,EGFR,ESR1,HIF1 A,CASP3,CTNNB1,VEGFA,MYC,PPARG,etc.may be the main potential targets of modified Huangqi-Guizhi-Wuwu Decoction in the treatment of diabetes nephropathy.(4)GO analysis shows that the functions with a large number of enrichment include RNA polymerase II,DNA binding transcription factors,nuclear receptors,etc.(5)KEGG enrichment analysis shows that these pathways are mainly enriched in lipids and atherosclerosis,human cytomegalovirus infection,hepatitis B,PI3K-Akt signaling pathway,AGE-RAGE signaling pathway,p53 signaling pathway,etc.in diabetes complications.Conclusion:1.Modified Huangqi-Guizhi-Wuwu Decoction can significantly improve the renal function of patients with diabetes nephropathy,reduce the quantitative level of 24-hour urinary protein,regulate the metabolism of triglycerides and cholesterol.2.It preliminarily verified the rationality and scientificity of the treatment of DN patients with modified Huangqi-Guizhi-Wuwu Decoction,suggesting that the treatment may take effect through quercetin,kaempferol,luteolin,ursolic acid,tanshinone IIA and other components,and through ALB,IL6,EGFR,ESR1,HIF1 A,CASP3,CTNNB1,VEGFA,MYC,PPARG and PI3K-Akt signal pathway,AGE-RAGE signal pathway,p53 signal pathway,etc.may be the main signal pathway of Modified Huangqi-Guizhi-Wuwu Decoction acting on DN.