滋肾祛瘀解毒方调控Nrf2/HO-1信号通路减轻子宫内膜异位症大鼠氧化应激的机制研究OA

Objective To investigate the effect of Zishen Quyu Jiedu Formula(滋肾祛瘀解毒方,ZQJF)on endometriosis(EMs)by regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway and to elucidate the thera-peutic mechanism from the perspective of oxidative stress.Methods Forty healthy non-pregnant female Sprague-Dawley(SD)rats were randomly divided into four groups(n=10 per group):sham-operated control,model(EMs),mifepristone,and ZQJF treatment.An EMs rat model was established via autologous endometrial transplantation.Hematoxylin-eosin(HE)staining was used to observe mor-phological changes in ectopic lesions.Immunohistochemistry(IHC)was performed to assess the positive expression of Nrf2,HO-1,and NAD(P)H quinone dehydrogenase 1(NQO1).Serum levels of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),8-epi-prostaglandin F2α(8-epi-PGF2α),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and estradiol(E2)were measured by enzyme-linked immunosorbent assay(ELISA).Western blot(WB)was conducted to determine the protein expression levels of Nrf2,HO-1,NQO1,and Kelch-like ECH-associated protein 1(KEAP1)in endometrial tissues.Results Compared with the model group,the ZQJF and mifepristone groups showed significantly increased serum levels of SOD and GSH-Px(P<0.01),while levels of MDA,8-epi-PGF2α,and E2 were decreased(P<0.05).The volume of ectopic lesions was significantly reduced.Stromal cells in the ectopic tissue were more orderly arranged with attenuated inflammatory cell infiltration.The positive expression areas for Nrf2 and NQO1 were enlarged,and the protein expression levels of Nrf2,HO-1,and NQO1 were markedly upregu-lated(P<0.01).Conclusion ZQJF can alleviate endometriosis progression by mediating the Nrf2/HO-1 signaling pathway,which reduces inflammatory cell infiltration and promotes atrophy in ectopic endometrial tissues.This effect is associated with enhanced anti-oxidant expression of Nrf2,NQO1,and HO-1.These findings provide a scientific basis for further research on EMs.