华良姜素对PDGF-BB诱导血管平滑肌细胞增殖和迁移的影响
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(1.菏泽医学专科学校基础医学部,山东省菏泽市274000;2.山东第一医科大学 山东省医学科学院 临床与基础医学院,山东省济南市250000)

作者简介:

李岩,博士,副教授,主要从事囊泡运输研究,E-mail:tracylee08@163.com。通信作者宋国华,博士,教授,博士研究生导师,主要从事脂质脂蛋白代谢与氢分子生物医学研究,E-mail:girl_sapphire@163.com。

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基金项目:

国家自然科学基金(81873517和81670422);山东省中医药科技发展计划项目(2019-0320);山东省泰山学者专项基金(tsqn20161045);山东省医药卫生科技发展计划项目(2018WS494)


Effects of jaranol on proliferation and migration of vascular smooth muscle cells induced by PDGF-BB
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1.Basic Medicine Department, Heze Medical College, Heze, Shandong 274000, China;2.School of Basic Medical Sciences, Shandong First Medical University &Shandong Academy of Medical Science, Jinan, Shandong 250000, China)

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    摘要:

    目的]探讨华良姜素对PDGF-BB诱导下血管平滑肌细胞增殖和迁移的影响及可能的机制。 [方法]利用25 μg/L的PDGF-BB处理人主动脉血管平滑肌细胞(HA-VSMC)诱导血管平滑肌细胞增殖和迁移。实验分为正常对照组、PDGF-BB组(模型组)、PDGF-BB+华良姜素(10、20、40 μmol/L)组和DMSO组。采用CCK-8实验检测HA-VSMC增殖活力,Transwell实验检测HA-VSMC迁移能力,Western blot检测自噬效应蛋白p62、LC3、雷帕霉素靶蛋白(mTOR)以及磷酸化mTOR(p-mTOR)蛋白表达水平的变化。 [结果]PDGF-BB处理后,HA-VSMC增殖和迁移能力显著上调(P<0.01),华良姜素显著抑制PDGF-BB诱导的HA-VSMC的增殖和迁移,且随浓度的上升抑制能力越明显(P<0.05)。与模型组比较,40 μmol/L华良姜素处理后,LC3Ⅰ以及mTOR蛋白表达水平显著降低(P<0.05);LC3Ⅱ/LC3Ⅰ、p62与p-mTOR蛋白表达水平显著升高(P<0.05),同时发现40 μmol/L华良姜素与AMPK抑制剂Compound C,对PDGF-BB诱导的HA-VSMC AMPK/mTOR信号通路的影响一致。 [结论]华良姜素可抑制PDGF-BB诱导的HA-VSMC的增殖和迁移,其作用机制可能是通过上调AMPK/mTOR信号通路,抑制自噬实现。

    Abstract:

    Aim To investigate the effect of jaranol on platelet derived growth factor-BB (PDGF-BB)-induced proliferation and migration of vascular smooth muscle cell(VSMC) as well as its possible mechanism. Methods Human aortic vascular smooth muscle cells (HA-VSMC)were treated with 25 μg/L PDGF-BB to induce proliferation and migration. The cells were divided into normal control group (NC group), PDGF-BB group, PDGF-BB+jaranol (0,0 and 40 μmol/L) group, DMSO group. Cell counting Kit-8 (CCK-8) assay was used to assess proliferation ability of HA-VSMC, and Transwell assay was used to examin the migration ability of HA-VSMC. Western blot was used to detect the expression of autophagy related proteins including p62, LC3, mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR). Results After treatment with PDGF-BB, the proliferation and migration ability of HA-VSMC was notably upregulated (P<0.01), while jaranol showed a significant and concentration-dependent inhibition effect on PDGF-BB-induced proliferation and migration of HA-VSMC (P<0.05). Western blot results showed that compared with the PDGF-BB group, the protein expression levels of LC3Ⅰ and mTOR were significantly decreased in PDGF-BB+jaranol (40 μmol/L) group (P<0.05); The expression levels of LC3Ⅱ/LC3Ⅰ, p62 and p-mTOR proteins were significantly increased (P<0.05), and the effect of jaranol(40 μmol/L) and compound C on AMPK/mTOR signaling pathway of HA-VSMC induced by PDGF-BB was consistent. Conclusion Jaranol can inhibit the abnormal proliferation and migration of HA-VSMC invoked by PDGF-BB, its mechanism may be related to its inhibition effect of PDGF-BB-induced autophagy of HA-VSMC by regulating AMPK/mTOR signaling pathway.

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李岩,安芸,张赫彬,张海燕,张凤英,宋国华.华良姜素对PDGF-BB诱导血管平滑肌细胞增殖和迁移的影响[J].中国动脉硬化杂志,2023,(10):865~871.

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  • 收稿日期:2023-06-02
  • 最后修改日期:2023-09-11
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  • 在线发布日期: 2023-11-08