间质性膀胱炎（IC）是一种慢性疼痛综合征，其特征为排尿频繁、急迫感和膀胱或盆底疼痛，严重影响患者的生活质量。本研究旨在调查长非编码RNA母亲表达基因3（lncRNA MEG3）在IC中的作用和机制。使用环磷酰胺腹腔注射结合番茄素和肿瘤坏死因子-α（TNF-α）膀胱灌注建立IC大鼠模型，以模拟IC。使用TNF-α诱导的大鼠膀胱上皮细胞建立体外模型。使用H＆E染色评估膀胱组织损伤，使用ELISA测量炎性细胞因子水平。使用Western blot分析Nrf2、Bax、Bcl-2、cleaved caspase-3、p-p38、p38、p-NF-κB和NF-κB蛋白质表达水平。RNA免疫沉淀和RNA pull-down试验用于检查MEG3和Nrf2之间的相互作用。在IC组织和膀胱上皮细胞中，MEG3水平上调，而发现Nrf2表达下调。抑制MEG3可以减轻膀胱组织损伤、炎症、氧化应激和细胞凋亡。MEG3与Nrf2呈负相关。降低MEG3可以通过上调Nrf2和抑制p38 / NF-κB信号通路来缓解IC炎症和损伤。降低MEG3通过上调Nrf2和抑制p38 / NF-κB通路缓解IC大鼠中的炎症和损伤。Copyright © 2023 Elsevier Ltd.保留所有权利。

Interstitial cystitis (IC), a chronic pain syndrome characterized by urinary frequency, urgency, and bladder or pelvic floor pain, severely affects the quality of life of patients. The aim of this study was to investigate the role and mechanism of long noncoding RNA Maternally Expressed Gene3 (lncRNA MEG3) in IC.An IC rat model was established by intraperitoneal injection of cyclophosphamide combined with bladder perfusion of fisetin and tumor necrosis factor-α (TNF-α) to mimic IC. An in vitro model was established using TNF-α-induced rat bladder epithelium cells. H&E staining was used to assess bladder tissue damage and ELISA was used to measure inflammatory cytokine levels. Western blot analysis was used to examine Nrf2, Bax, Bcl-2, cleaved caspase-3, p-p38, p38, p-NF-κB and NF-κB protein expression levels. RNA immunoprecipitation and RNA pull-down assays were used to examine the interaction between MEG3 and Nrf2.MEG3 levels were upregulated in IC tissues and bladder epithelial cells, whereas Nrf2 expression was found to be downregulated. Knockdown of MEG3 reduced bladder tissue injury, inflammation, oxidative stress and apoptosis. MEG3 was negatively correlated with Nrf2. Downregulation of MEG3 alleviated IC inflammation and injury by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.Downregulation of MEG3 alleviated inflammation and injury in IC rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.Copyright © 2023 Elsevier Ltd. All rights reserved.