基础医学与临床 ›› 2015, Vol. 35 ›› Issue (10): 1303-1307.

• 研究论文 •    下一篇

YC-1对低氧诱导人肺动脉平滑肌细胞增殖和p53表达的影响

李明星,蒋德旗,王艳,马艳娇,喻珊珊,王勇   

  1. 南方医科大学珠江医院
  • 收稿日期:2015-04-09 修回日期:2015-07-01 出版日期:2015-10-05 发布日期:2015-09-30
  • 通讯作者: 王勇 E-mail:ywang1120@126.com
  • 基金资助:
    SIRT6在低氧性肺动脉高压肺血管重构中的作用及机制研究;SIRT6在低氧性肺动脉高压中的作用研究

Effect of YC-1 on the hypoxia-induced proliferation of HPASMCs and the p53 expression

  • Received:2015-04-09 Revised:2015-07-01 Online:2015-10-05 Published:2015-09-30

摘要: 目的 研究低氧诱导因子(HIF-1α)抑制剂3-(5’-羟甲基-2’-呋喃基)-1-苯甲基吲唑(YC-1)对低氧诱导人肺动脉平滑肌细胞增殖、凋亡以及p53表达的影响,并探讨其相关分子机制。方法 体外培养人肺动脉平滑肌细胞(HPASMCs),将细胞分为常氧组、低氧组及低氧+ YC-1(0.01和0.05mmol/L)组;用CCK-8法及流式细胞仪检测细胞的增殖与凋亡,Western-blot法检测HIF-1α和p53蛋白的表达,RT-PCR检测p53 mRNA的表达;结果 低氧能够促进HPASMCs的增殖;不同浓度的YC-1处理24h后,HPASMCs增殖率显著下降(P<0.05),凋亡率显著升高(P<0.05);YC-1能降低HIF-1α蛋白的表达,上调p53的表达(P<0.05);结论 YC-1能抑制低氧诱导HPASMCs增殖,促进细胞凋亡,其作用机制可能与上调p53表达有关。

关键词: YC-1, 人肺动脉平滑肌细胞, 增殖, 凋亡, p53

Abstract: Objective To investigate the effects of hypoxia-inducible factor-1 alpha (HIF-1α) inhibitor YC-1 on hypoxia induced human pulmonary artery smooth muscle cells (HPASMCs) proliferation, apoptosis and the expression of p53, and explore the molecular mechanism in the processes. Method HPASMCs were cultured in DMEM medium supplemented with 10%FBS in vitro. Then divided them into four groups: normoxia, hypoxia and hypoxia+YC-1(0.01 and 0.05mmol/L). Cells proliferation was measured by CCK-8, and the apoptosis was detected by flow cytometry. The expression of HIF-1α and p53 were tested by Western Blot, and the mRNA expression of p53 was tested by RT-PCR. Results Hypoxia can promote the proliferation of HPASMCs. Treatment of HPASMCs with different concentrations of YC-1 intervention for 24h obviously dropped proliferation rate (P<0.05), and the apoptosis rate increased significantly (P<0.05). YC-1 can also down-regulate the expression of HIF-1α and up-regulate the expression of p53 significantly (P<0.05). Conclusion YC-1 can inhibit hypoxia-induced HPASMCs proliferation and promote apoptosis, and the mechanism probably related to the up-regulation of p53 expression.

Key words: YC-1, HPASMCs, Proliferation, Apoptosis, p53

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