Department of Reproductive Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Gynecology and Obstetrics, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
J Biochem Mol Toxicol. 2022 Dec;36(12):e23203. doi: 10.1002/jbt.23203. Epub 2022 Sep 3.
The protective effects of epigallocatechin-3-gallate (EGCG) on lipopolysaccharide (LPS)-induced endometritis in vivo and in vitro will be explored in this study. The endometritis model was induced in female BALB/c mice uterus by perfusion with lipopolysaccharide (LPS) and EGCG were administered at 1 h before LPS induction. The primary bovine endometrial epithelial cells (BEECs) were treated with EGCG for 1 h before LPS stimulation. Uterine histopathological changes, myeloperoxidase (MPO) activity, inflammatory cytokine levels and oxidative stress markers were determined. The extent of Bax, Bcl-2, cleaved caspase-3, silent information regulator transcript-1 (SIRT1), nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase1 was detected by Western blot and real-time quantitative PCR assays. The results showed that EGCG significantly reversed the LPS-induced uterine histopathological changes, MPO activity, pro-inflammatory cytokine levels. Additionally, EGCG decreased oxidative stress and reduced cell apoptosis by upregulating SIRT1 expression, downregulating the NLRP3 inflammasome activation. These findings indicated that EGCG exerted its greatest protective effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the SIRT1/NLRP3, making its promising candidate treatment for endometritis.
本研究旨在探讨表没食子儿茶素没食子酸酯(EGCG)对体内和体外脂多糖(LPS)诱导的子宫内膜炎的保护作用。通过向雌性 BALB/c 小鼠子宫内灌注 LPS 来诱导子宫内膜炎模型,并在 LPS 诱导前 1 小时给予 EGCG。在 LPS 刺激前用 EGCG 处理原代牛子宫内膜上皮细胞(BEEC) 1 小时。测定子宫组织病理学变化、髓过氧化物酶(MPO)活性、炎症细胞因子水平和氧化应激标志物。通过 Western blot 和实时定量 PCR 检测 Bax、Bcl-2、cleaved caspase-3、沉默信息调节转录因子 1(SIRT1)、核苷酸寡聚化结构域(NOD)样受体含pyrin 结构域 3(NLRP3)、凋亡相关斑点样蛋白(ASC)和 Caspase1 的表达水平。结果表明,EGCG 显著逆转了 LPS 诱导的子宫组织病理学变化、MPO 活性和促炎细胞因子水平。此外,EGCG 通过上调 SIRT1 表达、下调 NLRP3 炎性小体激活,降低氧化应激和细胞凋亡。这些发现表明,EGCG 通过阻断炎症反应、降低氧化应激和减少细胞凋亡发挥最大的保护作用,通过 SIRT1/NLRP3 途径,使其成为子宫内膜炎有前途的治疗候选药物。