Exploring the Mechanism of Fuzheng Huayu Formula in Intervening Angiogenesis in Endometriosis Based on Bioinformatics and Animal Experiments
ZHAO Jiajing
HUANG Yuxiao
ZHANG Yuqing
WANG Haixia
ZHU Youhua
BU Mengya
FANG Mengxin
XI Yanxue
Abstract：Objective Fuzheng Huayu(FZHY)formula has clear clinical efficacy in the treatment of endometriosis(EM).Previous studies confirmed that its mechanism may be related to the inhibition of angiogenesis.This study focused on this research hotspot to explore the mechanism of FZHY formula in treating EM.Methods The study was divided into two parts.The first part involved bioinformatics analysis.We obtained the drug targets of FZHY formula,the differentially expressed genes in EM,and angiogenesis-related targets,and identified the top 6"EM core targets".The expression matrices of normal and model group samples for these"EM core targets"were obtained from the GSE58178 microarray.A differential group comparison diagram was plotted,a TF-mRNA-miRNA network was constructed,and the core targets of action were screened.The second part consisted of animal experiment validation.An EM rat model was established by allogeneic endometrial transplantation.Model rats were divided into the model group,the Chinese medicine group(FZHY group),and the positive control group,with 6 rats in each group.A sham-operated group(n=6)was set as control.After 14 days of gavage treatment,samples were collected.Serum and endometrial tissues were examined.Enzyme-linked immunosorbent assay was used to detect serum levels of carbohydrate antigen 125(CA125)and vascular endothelial growth factor(VEGF).Reverse transcription quantitative real-time polymerase chain reaction was used to measure the mRNA expression of miR-199a-5p,hypoxia-inducible factor 1α(HIF-1α),VEGF and other related molecules in normal/ectopic endometrial tissues.Results Bioinformatics analysis indicated that in the key process of angiogenesis,FZHY formula may interfere with EM angiogenesis and slow the growth of ectopic lesions by downregulating HIF-1α,VCAM1,STAT3,and SERPINE1,and upregulating MMP2 and PDGFRB.Subsequently,through construction of the"TF-mRNA-miRNA network"and verification by animal experiments,compared with the model group,the Chinese medicine group showed significantly lower serum CA125 and VEGF levels,significantly reduced volume of ectopic lesions,increased expression of miR-199a-5p,and decreased expression of HIF-1α and VEGF[(9.99±1.01)U/mL vs(14.60±0.65)U/mL,P<0.05;(170.04±29.40)pg/mL vs(245.42±36.10)pg/mL,P<0.05;(6.41±2.11)mm³ vs(23.92±4.63)mm³,P<0.05;0.80±0.08 vs 0.02±0.01,P<0.05;1.28±0.06 vs 2.21±0.32,P<0.05;1.29±0.23 vs 3.79±0.80,P<0.05].Conclusion FZHY formula may intervene in the key process of angiogenesis by downregulating the expression of factors such as HIF-1α and VEGF,thereby shrinking EM ectopic lesions and delaying the further progression of EM.
Keywords：endometriosisFuzheng Huayu formulaangiogenesisbioinformaticsanimal experiment
Publication Date：2026-02-20
Online Publishing Date：2026-03-16(First online date of this platform, not the publication date of the document)
Pages：9( 286-294 )