补肾解毒汤调节MMP-9/TIMP-1平衡、抑制炎症反应并改善肾纤维化的效果评价OA

Objective To evaluate the clinical efficacy of Bushen Jiedu Decoction in the treatment of chronic kidney disease(CKD)stages 3-5 based on clinical data and network pharmacology prediction outcomes,and to explore its regulatory effects on key inflammatory and fibrotic targets.Methods Clinical data of 271 patients with CKD stages 3-5 were retro-spectively analyzed to evaluate the clinical efficacy of Bushen Jiedu Decoction.Network pharmacology methods were em-ployed:active components and corresponding targets of Bushen Jiedu Decoction were collected through the Traditional Chi-nese Medicine Systems Pharmacology(TCMSP)database and analysis platform,and CKD-related targets were screened from databases including Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),and Gene-Cards;intersecting targets were identified as candidate targets.A protein-protein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)platform,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed using the Database for Annotation,Visualization and Integrated Discovery(DAVID)to identify potential core pathways.Based on these findings,a randomized,single-blind,double-dummy,positive drug parallel-controlled trial was conducted,enrolling 82 patients with CKD stages 3-5,who were randomly assigned(in a 1∶1 ratio)to a study group(n=41)and a control group(n=41).The study group received Bushen Jiedu Decoction plus Niaoduqing Granule placebo,while the control group received Niaodu-qing Granule plus Bushen Jiedu Decoction placebo,with a treatment course of 8 weeks.Renal function indicators(serum creatinine[Scr],blood urea nitrogen[BUN],serum cystatin C[Cys-C],estimated glomerular filtration rate[eGFR])and serum levels of transforming growth factor-β1(TGF-β1),matrix metalloproteinase-9(MMP-9),tissue inhibitor of metallo-proteinase-1(TIMP-1),interleukin-10(IL-10),and interleukin-6(IL-6)were compared between the two groups before and after treatment,and adverse events were recorded.Results The retrospective analysis showed that the overall response rate of Bushen Jiedu Decoction in treating CKD patients was 70.1%,with significant improvements in renal function indicators after treatment(P<0.05)and a significant increase in eGFR(P<0.05),with no marked adverse reactions.Network pharmacology analysis suggested that potential core targets of Bushen Jiedu Decoction included CASP3,HIF1A,TP53,STAT3,AKT1,MMP9,MAPK3,PPARG,ESR1,TGFB1,etc.,with enriched pathways concentrated in typical in-flammatory-fibrotic axes,such as TNF,MAPK,and PI3K-Akt.The randomized controlled trial further confirmed that af-ter treatment,the improvement in renal function indicators in the study group was significantly better than that in the con-trol group(P<0.05);after treatment,serum levels of TGF-β1,TIMP-1,IL-10,and IL-6 in the study group decreased,while MMP-9 levels increased,with changes significantly greater than those in the control group(P<0.05),which was highly consistent with the network pharmacology predictions.Conclusion Bushen Jiedu Decoction can significantly strengthen renal function in patients with CKD stages 3-5,with particularly notable efficacy in those with CKD stages 3a and 3b,and has a good safety profile.Its mechanism of action may be related to the regulation of inflammatory responses and the inhibition of pathways associated with renal fibrosis.