早期诊断和治疗子宫内膜增生症（EH）对预防子宫内膜癌（EC）仍然是必要的。本研究旨在探讨二十碳五烯酸（EPA）对大鼠雌二醇戊酸酯（EV）引发的EH可能的保护作用。 成年雌性Wistar大鼠在接受EV治疗十天期间，同时或不同时接受EPA。利用生理学方法（重量指数）和组织病理学方法评估宫腔变化。评定异构体丙二醛（MDA）和血清总抗氧化能力（TAC），以及血清雌二醇和孕激素水平，以及细胞凋亡（宫腔内半胱氨酸蛋白酶-3）。通过免疫组化方法评估核因子κB（NF-κB）和血管内皮生长因子（VEGF）的估计值，以及在宫腔组织中诱导因子1α（HIF-1α）免疫印迹的测量值。 EV导致宫腔重量指数显著增加，伴随着EH的病理学证据。这些变化与明显的氧化应激标志物改变有关，调节雌二醇和孕激素血清水平，HIF-1α，NF-κB和VEGF免疫表达增加和半胱氨酸蛋白酶-3显著下降。EPA在任何剂量下都显著改善了宫腔重量指数以及组织病理变化。这种作用伴随着测量的激素水平、氧化应激、凋亡和炎症参数的显著改善。 EPA在使用的剂量下，通过调节NF-κB/HIF-1α/VEGF信号通路，在EV引发的EH中提供了生化和组织病理学的改善作用。版权所有©2023 Elsevier B.V.。保留所有权利。

Early diagnosis and treatment of endometrial hyperplasia (EH) remains mandatory for endometrial cancer (EC) prevention.To study the possible protective effect of eicosapentaenoic acid (EPA) in EH - induced by estradiol valerate (EV) in rats.Adult female Wistar rats were given EV with or without EPA for 10 days. The uterine changes were evaluated by both physical (weight index) and histopathological methods. The markers of oxidative stress (Uterine malondialdehyde (MDA) and serum total antioxidant capacity (TAC) as well as serum estradiol and progesterone levels, and apoptosis (uterine caspase-3) were determined. Immunohistochemical estimations of nuclear factor kappa B (NF-κB) and vascular endothelial growth factor (VEGF) in addition to hypoxia-inducible factor 1 alpha (HIF-1α) immunoblotting were measured in uterine tissue.EV showed significant increase in uterine weight index that is accompanied with histopatholigical evidences of EH. Such changes were associated with significant alterations in oxidative stress markers, modulation of estradiol and progesterone serum levels, an increase in HIF-1α, NF-κB and VEGF immuno-expressions and a significant decrease in caspase-3. EPA, in either dose, showed significant amelioration in uterine weight index as well as in histopathological changes. Such effect was accompanied with significant improvement in the measured hormonal levels, oxidative stress, apoptosis, and inflammatory parameters.EPA in the used doses provided biochemical and histopathological improvement in EV-induced EH via modulation of NF-κB/HIF-1α/VEGF signaling pathway.Copyright © 2023 Elsevier B.V. All rights reserved.