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氟伏沙明通过改善CD-MPR、KISS-1、水通道蛋白4(AQP4)和闭合蛋白-1(Claudin-1)的表达来抑制NLRP3和NF-κB炎症通路并维持生殖功能。

Fluvoxamine Inhibited NLRP3 and NF-κB Inflammatory Pathways and Maintained Genital Functions by Ameliorating CD-MPR, KISS-1, AQP4 and Claudin-1 Expressions.

作者信息

Topsakal Senay, Ozmen Ozlem, Ozcan Kadriye Nilay, Asci Halil, Imeci Orhan Berk, Sevuk Mehmet Abdulkadir, Kosar Pinar Aslan

机构信息

Department of Endocrinology and Metabolism, Faculty of Medicine, Pamukkale University, Denizli, Türkiye.

Department of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, Türkiye.

出版信息

Basic Clin Pharmacol Toxicol. 2025 Mar;136(3):e70000. doi: 10.1111/bcpt.70000.

Abstract

Fluvoxamine (FLV), a selective serotonin reuptake inhibitor, is commonly used to treat anxiety, major depressive disorder and obsessive-compulsive disorder, among other psychiatric conditions. This study aims to evaluate the effectiveness of FLV in mitigating damage caused by lipopolysaccharide (LPS) to the female genital tract. Thirty-two female Wistar Albino rats were randomly divided into four groups: control, LPS, LPS-FLV and FLV. At the end of the experimental period, tissues from the ovaries, fallopian tubes and uterus were collected for histological, immunohistochemical and genetic analyses. Histological examination of the LPS group revealed mild to moderate bleeding, oedema and neutrophil infiltration. Additionally, there were signs of endometrial damage in the uterus and loss of cilia in the fallopian tubes. Immunohistochemical analysis showed that LPS increased the expressions of nuclear factor kappa beta (NF-κB) and cation-dependent mannose 6-phosphate receptors (CD-MPR) and reduced kisspeptin-1 (KISS-1) expression. Genetic analysis indicated that LPS increased the expression of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) and aquaporin4 (AQP4) genes while decreasing Claudin-1 expression. However, all these adverse effects were reversed by FLV treatment. The study's findings suggest that FLV may be beneficial in treating LPS-induced damage to the female reproductive system.

摘要

氟伏沙明(FLV)是一种选择性5-羟色胺再摄取抑制剂,常用于治疗焦虑症、重度抑郁症和强迫症等多种精神疾病。本研究旨在评估氟伏沙明减轻脂多糖(LPS)对雌性生殖道造成损伤的有效性。将32只雌性Wistar白化大鼠随机分为四组:对照组、LPS组、LPS-FLV组和FLV组。实验期结束时,收集卵巢、输卵管和子宫组织进行组织学、免疫组织化学和基因分析。LPS组的组织学检查显示有轻度至中度出血、水肿和中性粒细胞浸润。此外,子宫存在子宫内膜损伤迹象,输卵管出现纤毛缺失。免疫组织化学分析表明,LPS增加了核因子κB(NF-κB)和阳离子依赖性甘露糖6-磷酸受体(CD-MPR)的表达,并降低了亲吻素-1(KISS-1)的表达。基因分析显示,LPS增加了含NOD样受体家族吡啉结构域3(NLRP3)和水通道蛋白4(AQP4)基因的表达,同时降低了闭合蛋白-1的表达。然而,氟伏沙明治疗可逆转所有这些不良反应。该研究结果表明,氟伏沙明可能有助于治疗LPS诱导的雌性生殖系统损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bafe/11786297/0cd4259e2354/BCPT-136-0-g003.jpg

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