Clinical Observation And Network Pharmacological Analysis Of Guiqi Zhenwu Tang In The Treatment Of Idiopathic Membranous Nephropathy

Objective:To observe the clinical efficacy and safety of Guiqi Zhenwu Tang in the treatment of idiopathic membranous nephropathy phase SⅠ-Ⅱ.(mutual evidence of spleen and kidney yang deficiency and stasis water),and at the same time use network pharmacology to explore the possible mechanism of action of Guiqi Zhenwu Tang in the treatment of idiopathic membranous nephropathy,so as to provide more objective and accurate data support and new clinical ideas for the treatment of idiopathic membranous nephropathy.Methods: In this study,66 patients who met the inclusion criteria were randomly grouped into 33 cases in the test group and 33 cases in the control group.The control group was given western basic treatment plus tacrolimus combined with hormone treatment,while the test group was treated with Guiqi Zhenwu Tang on top of the control group.The differences between 24-hour urine protein quantification(24h UP),serum albumin(Alb),antiphospholipase A2 receptor antibody(PLA2R-Ab),triglycerides(TG),cholesterol(TC),D-dimer(D-D),fibrinogen(Fib),and TCM syndrome integrals were observed in the two groups,and statistical analysis and safety evaluation were carried out.Network pharmacology part: through multiple databases to screen the compound components of Guiqi Zhenwu Tang and predict the gene target,through the database screening of idiopathic membranous nephropathy disease-related genes,the use of Venny2.1.0 to take the intersection of the two gene information,the obtained target protein using String database to make protein-protein interaction network map,the use of KOBAS3.0 database for enrichment analysis.Results: Efficacy evaluation:(1)Overall clinical efficacy: The overall effective rate of the experimental group and the control group were78.13% and 51.61% respectively,and the overall efficacy of the experimental group was better than that of the control group(P<0.05).(2)Chinese medicine evidence efficacy: the total effective rate of the test group and the control group were 93.75% and 61.29% respectively,and the efficacy of the test group was significantly higher than that of the control group(P<0.01).(3)24h UP and Alb: After 4,8 and 12 weeks of treatment,both the test and control groups had higher levels of reduced24 h UP than before treatment(P<0.01);the test group had higher levels of reduced 24 h UP than the control group at 8 and 12 weeks of treatment(P<0.05).The control group had higher levels of elevated Alb after 4 weeks of treatment than before treatment(P<0.05);the control group had significantly higher levels of elevated Alb at 8 and 12 weeks of treatment and the test group had higher levels of elevated Alb after 4,8 and 12 weeks of treatment than before treatment(P<0.01);the test group had higher levels of Alb after 12 weeks of treatment than the control group(P<0.05).(4)PLA2R-Ab: There was a significant difference in the reduction of PLA2R-Ab titer in both groups after treatment compared with that before treatment(P < 0.01).The test group was better than the control group in terms of PLA2R-Ab titer reduction,and the difference was statistically significant(P < 0.05).(5)TG,TC,Fib,D-D: TG and TC in both groups were significantly different after the test compared to before the test(P< 0.01).The test group was higher than the control group in reducing TG and TC levels(P < 0.05).Fib and D-D in the test group were significantly lower after treatment compared to before treatment(P < 0.01),and the treatment effect of Fib in the test group was better than that of the control group(P < 0.05),and the treatment effect of D-D in the test group was better than that of the control group(P < 0.05).(6)Safety evaluation:There were no abnormal changes in vital signs,blood routine,urine routine,stool routine,liver and kidney function and electrocardiogram in both groups after treatment compared with those before treatment.Two patients in the control group developed drug-related hyperglycemia during the treatment and the symptoms disappeared after glucose-lowering treatment.Network pharmacological results: A total of 43 compound species that met the screening criteria,215 drug gene targets,4875 genes related to idiopathic membranous nephropathy were detected,and 135 gene names were obtained after intersecting with Guiqi Zhenwu Tang gene names.The proteinprotein interaction network constructed by the analysis screened 15 core targets,and 35 signal pathways were obtained by enrichment analysis.Conclusion: In this study,it was found that the addition of Guiqi Zhenwu Tang can reduce the urine protein,increase blood albumin,regulate immune response,improve blood hypercoagulability and lipid status,and significantly improve the symptoms of traditional Chinese medicine in IMN patients than tacrolimus and hormones alone.Based on network pharmacology,it was found that the main active ingredients of Guiqi Zhenwu Tang for the treatment of IMN were sitosterol,β-sitosterol,ivy saponins,catechins,kaempferol,paeoniflorins,and sterols.Guiqi Zhenwu Tang contains core gene targets such as TP53,AKT1,HSP90AA1,JUN,CCNA2,etc.And the results of path enrichment analysis show that MAPKs signaling pathway,PI3K-Akt signaling pathway and multiple cancer pathways may be the main pathways for Guiqi Zhenwu Tang to play a role.