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香桃木蜂蜜对双侧卵巢切除大鼠外阴阴道萎缩(VVA)的调节作用。

Modulation of vulvovaginal atrophy (VVA) by Gelam honey in bilateral oophorectomized rats.

机构信息

Faculty of Applied Sciences, School of Biological Sciences, Universiti Teknologi MARA, Shah Alam, Malaysia.

Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

出版信息

Front Endocrinol (Lausanne). 2023 Feb 27;14:1031066. doi: 10.3389/fendo.2023.1031066. eCollection 2023.

Abstract

INTRODUCTION

Vulvovaginal atrophy (VVA) is a common condition in post-menopausal women. Symptoms of VVA include dyspareunia, vaginal dryness, vaginal and/or vulvar itching, burning and soreness, dysuria and vaginal bleeding accompanying sexual activity. These symptoms are physiological responses to hypoestrogenicity, inducing atrophy of the vagina epithelia and sudden reduction in mucous production. Prevailing therapy for VVA is hormone replacement therapy (HRT), notably estrogen, progesterone or a combination of the two. However, using HRT is associated with an increased incidence of breast and endometrial cancer, venous thromboembolism in the lungs and legs, stroke and cardiovascular complications.

METHODS

This study evaluated Malaysian Gelam honey as a nutraceutical alternative to estrogen HRT (ERT) in alleviating VVA. A total of 24 female 8-weekold Sprague Dawley rats underwent bilateral oophorectomy. A minimum of 14 days elapsed from the time of surgery and administration of the first dose of Gelam honey to allow the female hormones to subside to a stable baseline and complete recovery from surgery. Vaginal tissues were harvested following a 2-week administration of Gelam honey, the harvested vagina tissue underwent immunohistochemistry (IHC) analysis for protein localization and qPCR for mRNA expression analysis.

RESULTS

Results indicated that Gelam honey administration had increased the localization of Aqp1, Aqp5, CFTR and Muc1 proteins in vaginal tissue compared to the menopause group. The effect of Gelam honey on the protein expressions is summarized as Aqp1>CFTR>Aqp5>Muc1.

DISCUSSION

Gene expression analysis reveals Gelam honey had no effect on Aqp1 and CFTR genes. Gelam honey had up-regulated Aqp5 gene expression. However, its expression was lower than in the ERT+Ovx group. Additionally, Gelam honey up-regulated Muc1 in the vagina, with an expression level higher than those observed either in the ERT+Ovx or SC groups. Gelam honey exhibits a weak estrogenic effect on the genes and proteins responsible for regulating water in the vaginal tissue (Aqp1, Aqp5 and CFTR). In contrast, Gelam honey exhibits a strong estrogenic ability in influencing gene and protein expression for the sialic acid Muc1. Muc1 is associated with mucous production at the vaginal epithelial layer. In conclusion, the protein and gene expression changes in the vagina by Gelam honey had reduced the occurrence of vaginal atrophy in surgically-induced menopause models.

摘要

简介

阴道萎缩(VA)是绝经后妇女的常见病症。VA 的症状包括性交痛、阴道干燥、阴道和/或外阴瘙痒、灼热和疼痛、排尿困难以及伴随性行为的阴道出血。这些症状是由于雌激素水平降低引起的阴道上皮萎缩和粘液分泌突然减少的生理反应。VA 的主要治疗方法是激素替代疗法(HRT),尤其是雌激素、孕酮或两者的结合。然而,使用 HRT 会增加乳腺癌和子宫内膜癌、肺和腿部静脉血栓栓塞、中风和心血管并发症的发病率。

方法

本研究评估了马来西亚珍珠兰蜂蜜作为雌激素 HRT(ERT)的替代疗法,以缓解 VA。共 24 只 8 周龄的 Sprague Dawley 大鼠接受双侧卵巢切除术。从手术和第一剂珍珠兰蜂蜜给药到女性激素降至稳定基线并从手术中完全恢复,至少需要 14 天。在给予珍珠兰蜂蜜 2 周后采集阴道组织,对采集的阴道组织进行免疫组织化学(IHC)分析以定位蛋白,并进行 qPCR 分析以检测 mRNA 表达。

结果

结果表明,与绝经组相比,珍珠兰蜂蜜给药增加了阴道组织中 Aqp1、Aqp5、CFTR 和 Muc1 蛋白的定位。珍珠兰蜂蜜对蛋白质表达的影响总结为 Aqp1>CFTR>Aqp5>Muc1。

讨论

基因表达分析显示,珍珠兰蜂蜜对 Aqp1 和 CFTR 基因没有影响。珍珠兰蜂蜜上调了 Aqp5 基因的表达。然而,其表达水平低于 ERT+Ovx 组。此外,珍珠兰蜂蜜在上调阴道中 Muc1 的表达,其表达水平高于 ERT+Ovx 或 SC 组。珍珠兰蜂蜜对负责调节阴道组织水分的基因和蛋白表现出较弱的雌激素效应(Aqp1、Aqp5 和 CFTR)。相比之下,珍珠兰蜂蜜在影响负责阴道上皮层粘蛋白 Muc1 基因和蛋白表达方面表现出很强的雌激素能力。Muc1 与阴道上皮层的粘液分泌有关。综上所述,珍珠兰蜂蜜通过改变阴道的蛋白质和基因表达,减少了手术诱导的绝经模型中阴道萎缩的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d35/10010262/4e08e90b1fc9/fendo-14-1031066-g001.jpg

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