黄酮哌酯通过抑制TGF-β1减轻双酚A诱导的前列腺纤维化

承德医学院学报 ›› 2026, Vol. 43 ›› Issue (4): 271-276.

• 基础医学 • 下一篇

黄酮哌酯通过抑制TGF-β1减轻双酚A诱导的前列腺纤维化

刘涵钰¹, 杨烨¹, 蔡斯宇¹, 刘明艳¹, 陈镜楼^1,2,3,*, 黄念芳^2,3

1.江汉大学医学部药学系,湖北武汉 430056;
2.江汉大学认知与情感障碍湖北省重点实验室,湖北武汉 430056;
3.江汉大学医学部湖北省医学实验教学示范中心,湖北武汉 430056

收稿日期:2025-07-09 出版日期:2026-08-25 发布日期:2026-08-31
通讯作者: *陈镜楼（1987—）,男,博士,副教授,研究方向：泌尿生殖系统疾病的药学研究;E-mail：jinglouchen@126.com。
作者简介:刘涵钰（2006—）,女,本科在读,研究方向：泌尿生殖系统疾病的药学研究。
基金资助:
江汉大学学生科研项目（2024zd061）; 江汉大学校级科研项目资助计划（2023KJZX23）

Flavoxate attenuates bisphenol A-induced prostatic fibrosis by inhibiting TGF-β1

LIU Hanyu¹, YANG Ye¹, CAI Siyu¹, LIU Mingyan¹, CHEN Jinglou^1,2,3,*, HUANG Nianfang^2,3

1. Department of Pharmacy, School of Medicine, Jianghan University, Hubei, Wuhan, 430056, China;
2. Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Hubei, Wuhan, 430056, China;
3. Hubei Provincial Demonstration Center for Experimental Center, School of Medicine, Jianghan University, Hubei, Wuhan, 430056, China

Received:2025-07-09 Online:2026-08-25 Published:2026-08-31

摘要/Abstract

摘要： 目的研究黄酮哌酯对双酚A（BPA）诱导的前列腺纤维化的抑制作用和机制。方法在动物水平通过每日灌胃10 µg·kg^-1的BPA建立大鼠BPA暴露模型,持续6周后,收集大鼠前列腺组织进行Masson和天狼猩红染色观察各组动物前列腺组织胶原沉积情况,并通过免疫组化和qPCR检测E-钙黏蛋白（E-cad）、波形蛋白（VIM）和α-平滑肌肌动蛋白（α-SMA）评估各组动物前列腺组织上皮–间质转化（EMT）程度。在细胞水平通过用100 nmol·L^-1的BPA孵育人前列腺上皮RWPE-1细胞建立前列腺细胞BPA暴露模型,通过qPCR检测α-SMA、E-cad及胶原相关基因Col1A1和Col3A1的mRNA水平,评价各组细胞胶原分泌和EMT的影响;并通过Western blot检测TGF-β1的蛋白表达水平,探讨黄酮哌酯的作用机制。结果在动物水平,黄酮哌酯在80或40 mg·kg^-1给药剂量下抑制BPA诱导的大鼠前列腺胶原沉积和EMT。在细胞水平,相较于模型组,50 µg·L^-1的黄酮哌酯显著降低RWPE-1细胞α-SMA、VIM、Col1A1和Col3A1的mRNA水平,并增加E-cad的mRNA水平,抑制TGF-β1的表达。且该效应在一定程度上被TGF-β通路激动剂抵消。结论黄酮哌酯通过降低TGF-β1的水平,抑制胶原沉积与EMT,改善BPA诱导的前列腺纤维化。

关键词: 黄酮哌酯, 双酚A, 前列腺, 纤维化, 上皮-间质转化

Abstract: Objective To study the inhibitory effect and mechanism of flavoxate on prostatic fibrosis induced by bisphenol A (BPA). Methods At the animal level, the BPA exposure model was established by orally administering 10 µg·kg^-1 BPA daily to rats for 6 weeks. Then, the rat prostates were collected to evaluate tissue collagen deposition by Sirius red and Masson staining, as well as to assess epithelial-mesenchymal transition (EMT) by immunohistochemistry analysis and quantitative real-time PCR (qPCR) analysis for E-cadherin (E-cad), vimentin (VIM) and α-smooth muscle actin (α-SMA). At the cellular level, the BPA exposure model was established by incubating human prostatic epithelial RWPE-1 cells with 100 nmol·L^-1BPA. The collagen secretion and EMT of RWPE-1 cells were evaluated by qPCR analysis for the mRNA levels of α-SMA, E-cad, Col1A1 and Col3A1. The mechanism of flavoxate was investigated by Western blot analysis for TGF-β1. Results At the animal level, daily treatment with 80 or 40 mg·kg^-1 flavoxate attenuated BPA-induced rat prostate collagen deposition and EMT. At the cellular level, compared with the model group, 50 µg·L^-1 flavoxate significantly downregulated α-SMA, VIM, Col1A1 and Col3A1 while upregulated E-cad in RWPE-1 cells, accompanied by suppression of TGF-β1. These effects were partially reversed by a TGF-β pathway agonist. Conclusion Flavoxate can improve BPA-induced prostatic fibrosis by suppressing TGF-β1 and inhibiting collagen deposition and EMT.

Key words: flavoxate, bisphenol A, prostate, fibrosis, epithelial-mesenchymal transition

中图分类号:

R697.3

刘涵钰, 杨烨, 蔡斯宇, 刘明艳, 陈镜楼, 黄念芳. 黄酮哌酯通过抑制TGF-β1减轻双酚A诱导的前列腺纤维化[J]. 承德医学院学报, 2026, 43(4): 271-276.

LIU Hanyu, YANG Ye, CAI Siyu, LIU Mingyan, CHEN Jinglou, HUANG Nianfang. Flavoxate attenuates bisphenol A-induced prostatic fibrosis by inhibiting TGF-β1[J]. Journal of Chengde Medical University, 2026, 43(4): 271-276.

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黄酮哌酯通过抑制TGF-β1减轻双酚A诱导的前列腺纤维化

Flavoxate attenuates bisphenol A-induced prostatic fibrosis by inhibiting TGF-β1

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