浙江大学学报（医学版）2026，Vol.55Issue(3)：246-255,10.DOI:10.3724/zdxbyxb-2025-0459
当归多糖通过抑制Keap1/Nrf2/HO-1介导的氧化应激恢复自噬稳态改善大鼠子宫内膜异位症
Angelica sinensis polysaccharide ameliorates endometriosis in rats by restoring autophagic homeostasis via inhibition of Keap1/Nrf2/HO-1-mediated oxidative stress
摘要
Abstract
Objective:To investigate the mechanism of Angelica sinensis polysac-charide(ASP)ameliorating endometriosis(EMT)via the Kelch-like epichlorohydrin-associated protein 1(Keap1)/nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Methods:SD rats were randomly divided into six groups(n=12 per group):normal control,model control,low-dose ASP,high-dose ASP,gestrinone,and high-dose ASP+recombinant Keap1(rKeap1).EMT models were established in all groups except the normal control group.After successful modeling,the drugs were administered once daily for 4 weeks.The mass and volume of ectopic endometrial tissue were measured.Histopathological changes were evaluated using hematoxylin and eosin staining.Levels of reactive oxygen species,malondialdehyde,and superoxide dismutase(SOD)were measured using commercial kits.The number of autophagosomes was examined under transmission electron microscopy.The relative fluorescence intensity of microtubule-associated protein light chain 3(LC3)in endometrial tissue was assessed by immunofluorescence staining.Western blotting was used to determine the protein expression levels of LC3-Ⅱ,LC3-Ⅰ,p62,Keap1,Nrf2 in the nucleus,and HO-1.Results:Compared with the normal control group,the model control group showed increased glandular proliferation,pronounced vacuolization of glandular cells,and substantial inflammatory cell infiltration in ectopic endometrial tissue.Levels of reactive oxygen species,malondialdehyde,p62,and Keap1 were significantly increased,while SOD levels,autophagosome numbers,and LC3 fluorescence intensity were significantly decreased(all P<0.05).Protein expression levels of LC3-Ⅱ/LC3-Ⅰ,Nrf2 in the nucleus,and HO-1 were also significantly reduced(all P<0.05).Compared with the model control group,the low-and high-dose ASP groups and the gestrinone group exhibited alleviated pathological damages,reduced mass and volume of ectopic endometrial tissues,decreased levels of reactive oxygen species,malondialdehyde,p62,and Keap1,and increased SOD levels,autophagosome numbers,LC3 fluorescence intensity,and protein expression levels of LC3-Ⅱ/LC3-Ⅰ,Nrf2 in the nucleus,and HO-1(all P<0.05).However,co-administration of rKeap1 reversed the inhibitory effects of high-dose ASP on oxidative stress and its restorative effects on autophagic homeostasis in EMT rats.Conclusion:Angelica sinensis polysaccharide may ameliorate EMT in rats by inhibiting Keap1-mediated activation of the Nrf2/HO-1 pathway,thereby suppressing oxidative stress and restoring autophagic homeostasis.关键词
子宫内膜异位症/当归多糖/氧化应激/自噬/Keap1/Nrf2/HO-1信号通路/大鼠Key words
Endometriosis/Angelica sinensis polysaccharide/Oxidative stress/Autophagy/Keap1/Nrf2/HO-1 signaling pathway/Rats分类
医药卫生引用本文复制引用
李捷,李潇,姬霞,黄瑶,王占利..当归多糖通过抑制Keap1/Nrf2/HO-1介导的氧化应激恢复自噬稳态改善大鼠子宫内膜异位症[J].浙江大学学报（医学版）,2026,55(3):246-255,10.基金项目
河南省科技攻关项目(232102310478)The study was supported by Key Science and Technology Project of Henan Province(232102310478) （232102310478）
