雌二醇和白藜芦醇二聚体对颏舌肌成肌细胞HIF-1α的作用及机制

doi:10.19439/j.sjos.2018.04.004

上海口腔医学 ›› 2018, Vol. 27 ›› Issue (4): 354-359.doi: 10.19439/j.sjos.2018.04.004

雌二醇和白藜芦醇二聚体对颏舌肌成肌细胞HIF-1α的作用及机制

李远远, 郝彤, 卢芸, 刘月华

上海市口腔病防治院口腔正畸科,复旦大学附属口腔医院口腔生物医学工程实验室,上海 200031

收稿日期:2017-08-24 修回日期:2017-11-27 出版日期:2018-08-25 发布日期:2018-10-09
通讯作者: 刘月华,E-mail：liuyuehua@fudan.edu.cn
作者简介:李远远（1989-）,女,博士,住院医师,E-mail：liyuanyuan831@sina.com
基金资助:
基金项目上海市科学技术委员会科研计划项目（15140903500）

Effect of 17β-estradiol or resveratrol dimer on hypoxia inducible factor-1α in genioglossus myoblasts and its mechanism

LI Yuan-yuan, HAO Tong, LU Yun, LIU Yue-hua

Department of Orthodontics, Shanghai Stomatological Disease Center; Oral Biomedical and Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University. Shanghai 200031, China

Received:2017-08-24 Revised:2017-11-27 Online:2018-08-25 Published:2018-10-09

摘要/Abstract

摘要： 目的: 研究雌二醇（17β-estrodial,E2）和白藜芦醇二聚体（resveratrol dimer,RD）对低氧诱导因子1α（hypoxia-inducible factor-1α, HIF-1α）的作用及其分子生物学机制。方法: 提取小鼠颏舌肌成肌细胞,构建ERα敲降的成肌细胞（KD组）低氧模型,将成肌细胞（NS组）和KD组细胞分别低氧、低氧+E2、低氧+RD或低氧++E2+LY294002处理24 h, 利用Western免疫印迹方法检测信号分子T-Akt和P-Akt的表达,qRT-PCR和 Western免疫印迹检测HIF-lα的表达水平。采用SPSS17.0软件包对数据进行统计学分析。结果: 低氧环境下成肌细胞HIF-1α的表达显著高于常氧（P<0.05）,E2或RD处理后,HIF-1α的表达水平显著低于低氧组（P<0.05）;ERα敲降后,低氧也促进HIF-1α的表达（P<0.05）,但是E2或RD+低氧处理组成肌细胞HIF-1α的表达与低氧相比无显著差异（P>0.05）,Western免疫印迹结果与RT-PCR结果趋势一致。PI3K/Akt通路抑制剂与E2共培养则促进HIF-1α的表达（P<0.05）。结论: ERα在E2或RD对小鼠颏舌肌成肌细胞HIF-1α的抑制中起主导作用,其下游PI3K/Akt信号通路在该抑制效应中也发挥重要作用。

关键词: 成肌细胞, 白藜芦醇二聚体, 雌激素受体α, 低氧诱导因子1α, PI3K/Akt

Abstract: PURPOSE: To investigate the role of 17β-estradiol (E2) and resveratrol dimer (RD) on HIF-1α and the underlying mechanism. METHODS: Mice genioglossus myoblasts were isolated and cultured, and the estrogen receptor-α (ERα) shRNA lentivirus was used for gene knockdown. Cells in different groups were treated with different agents (E2, or RD, or E2 and LY294002), then incubated in normoxia or hypoxia for 24 h, the expressions of HIF-1α, ERα, ERβ, total-Akt and phospho-Akt were detected using qRT-PCR and Western blot. Statistical analysis was completed with SPSS 17.0 software package. RESULTS: Both E2 and RD inhibited the overexpression of HIF-1α induced by hypoxia at mRNA and protein levels, and these effects were eliminated by genetic silencing of ERα by RNAi. Mechanically, E2 activated PI3K/Akt pathways to induce HIF-1α expression. CONCLUSIONS: ERα may be responsible for down-regulation of HIF-1α by E2 or RD via activation of downstream PI3K/Akt pathways.

Key words: Genioglossus myoblast, Resveratrol dimer, Estrogen receptor α, HIF-1α, PI3K/Akt

中图分类号:

R782.2

李远远, 郝彤, 卢芸, 刘月华. 雌二醇和白藜芦醇二聚体对颏舌肌成肌细胞HIF-1α的作用及机制[J]. 上海口腔医学, 2018, 27(4): 354-359.

LI Yuan-yuan, HAO Tong, LU Yun, LIU Yue-hua. Effect of 17β-estradiol or resveratrol dimer on hypoxia inducible factor-1α in genioglossus myoblasts and its mechanism[J]. Shanghai Journal of Stomatology, 2018, 27(4): 354-359.

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雌二醇和白藜芦醇二聚体对颏舌肌成肌细胞HIF-1α的作用及机制

Effect of 17β-estradiol or resveratrol dimer on hypoxia inducible factor-1α in genioglossus myoblasts and its mechanism

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