神经调节蛋白1通过ERK1-2通路减轻心肌细胞缺氧复氧损伤
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(武汉科技大学附属武昌医院心内科,湖北省武汉市 430063)

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黄县立,主治医师,研究方向为冠心病介入治疗,E-mail为93911325@qq.com。通信作者熊慧,硕士,副主任医师,研究方向为心脏康复,E-mail为877826737@qq.com。

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Neuregulin-1 alleviates hypoxia/reoxygenation injury of cardiomyocytes through ERK1/2 pathway
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Department of Cardiology, Wuchang Hospital of Wuhan University of Science and Technology, Wuhan, Hubei 430063, China)

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    摘要:

    目的 探究神经调节蛋白1(NRG-1)通过细胞外调节蛋白激酶1/2(ERK1/2)通路减轻心肌细胞缺氧复氧(H/R)损伤的作用。方法 培养心肌H9c2细胞株,随机分为常规条件下用不含药物DMEM处理的对照组、H/R条件下用不含药物DMEM处理的H/R组、H/R条件下用含NRG-1 DMEM处理的NRG-1组、H/R条件下用含NRG-1及ERK1/2抑制剂PD98059处理的NRG-1+PD组。检测细胞增殖活力、凋亡率及细胞中的凋亡基因、炎症指标、ERK1/2。结果 H/R组细胞的OD490水平明显低于对照组,细胞凋亡率、细胞中cleaved Caspase-8、cleaved Caspase-9、cleaved Caspase-3、核因子κB(NF-κB)、ERK1/2的表达水平及培养基中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、γ干扰素(IFN-γ)的含量明显高于对照组;NRG-1组细胞的OD490水平及细胞中ERK1/2的表达水平明显高于H/R组,细胞凋亡率、细胞中cleaved Caspase-8、cleaved Caspase-9、cleaved Caspase-3、NF-κB的表达水平及培养基中TNF-α、IL-1β、IFN-γ的含量明显低于H/R组;NRG-1+PD组细胞的OD490水平及细胞中ERK1/2的表达水平明显低于NRG-1组,细胞凋亡率、细胞中cleaved Caspase-8、cleaved Caspase-9、cleaved Caspase-3、NF-κB的表达水平及培养基中TNF-α、IL-1β、IFN-γ的含量明显高于NRG-1组。结论 NRG-1通过激活ERK1/2通路减轻心肌细胞H/R损伤。

    Abstract:

    Aim To investigate the effect of neuregulin-1(NRG-1) on alleviating hypoxia/reoxygenation (H/R) injury of cardiomyocytes through extracellular regulated protein kinase 1/2 (ERK1/2) pathway. Methods Myocardial H9c2 cell lines were cultured and randomly divided into control group treated with DMEM without drugs under conventional conditions, H/R group treated with DMEM without drugs under H/R conditions, NRG-1 group treated with DMEM containing NRG-1 under H/R conditions, and NRG-1+PD group treated with PD98059 containing NRG-1 and ERK1/2 inhibitors under H/R conditions. Then cell proliferation, apoptosis, apoptosis gene, inflammatory index, ERK1/2 were determined.Results The OD490 level of H/R group was significantly lower than that of control group, the apoptotic rate, the expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, nuclear factor kappa B (NF-κB), ERK1/2 in cells and the contents of tumor necrosis factor alpha (TNF-α), interleukin 1beta (IL-1β), interferon gamma (IFN-γ) in culture medium were significantly higher than those of control group. The OD490 level and the expression level of ERK1/2 in cells of NRG-1 group were significantly higher than those of H/R group, and the apoptotic rate, the expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, NF-κB in cells and the contents of TNF-α, IL-1β, IFN-γ in culture medium were significantly lower than those of H/R group. The OD490 level and the expression level of ERK1/2 in cells of NRG-1+PD group were significantly lower than those of NRG-1 group, and the apoptotic rate, the expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, NF-κB in cells and the contents of TNF-α, IL-1β, IFN-γ in culture medium were significantly higher than those of NRG-1 group. Conclusion NRG-1 can alleviate H/R injury of cardiomyocytes by activating ERK1/2 pathway.

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黄县立,饶玲璋,熊慧,张鹏.神经调节蛋白1通过ERK1-2通路减轻心肌细胞缺氧复氧损伤[J].中国动脉硬化杂志,2019,27(11):950~955.

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  • 收稿日期:2019-02-06
  • 最后修改日期:2019-04-03
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  • 在线发布日期: 2019-12-18