丹酚酸B介导巨噬细胞Piezo1/MAPK/YAP轴对动脉粥样硬化的保护作用
作者:
作者单位:

(1.广州中医药大学第一附属医院,广东省广州市510405;2.广州中医药大学岭南医学研究中心,广东省广州市510405;3.山东中医药大学中医药创新研究院,山东省济南市250355)

作者简介:

潘显梅,博士,主治医师,研究方向为中医药防治心血管疾病,E-mail:499190864@qq.com。通信作者李静,博士,研究员,博士研究生导师,研究方向为钙离子通道调控心血管疾病的机制及中医药干预,E-mail:bmsjingl@gzucm.edu.cn。

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基金项目:

国家自然科学基金面上项目(NSFC82174196);山东省自然科学基金重大基础研究项目(ZR2020ZD16);山东省自然科学基金青年项目(ZR2020QH340)


Protective effect of salvianolic acid B mediating the macrophages Piezo1/MAPK/YAP axis in regulating atherosclerosis
Author:
Affiliation:

1.The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China;2.Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China;3.Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China)

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    摘要:

    目的]探讨丹酚酸B对氧化型低密度脂蛋白(ox-LDL)诱导的泡沫细胞形成在动脉粥样硬化中的保护作用。 [方法]提取小鼠骨髓来源巨噬细胞(BMDM),用50 mg/L氧化型低密度脂蛋白(ox-LDL)诱导泡沫细胞模型,同时加入Piezo1通道激动剂Yoda1观察与Piezo1相关性,药物组加入不同浓度的丹酚酸B处理。采用油红O染色法检测各组细胞脂质含量,Western blot法检测肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)和白细胞介素6(IL-6)等炎症因子的蛋白表达水平,以及YAP及MAPK级联蛋白表达水平,免疫荧光法检测YAP蛋白核易位表达。 [结果]Yoda1干预组的泡沫细胞形成显著增加(P<0.05);与Yoda1干预组比较,SalB组明显抑制泡沫细胞形成(P<0.05)。与正常对照组比较,模型组炎症因子蛋白表达升高,而Yoda1干预组升高更明显,SalB组炎症因子蛋白表达水平明显降低,差异具有统计学意义(P<0.05)。此外,模型组细胞YAP蛋白明显向核内易位,而Yoda1干预组向核内易位更明显,差异具有统计学意义(P<0.05),SalB组YAP蛋白向细胞核内易位明显减少。同时,模型组和Yoda1干预组细胞磷酸化P38、ERK1/2、JNK蛋白表达升高,SalB组磷酸化P38、ERK1/2、JNK蛋白表达明显降低,差异具有统计学意义(P<0.05)。 [结论]丹酚酸B抑制ox-LDL及Yoda1诱导的泡沫细胞形成,抑制炎症因子的蛋白表达水平,从而延缓动脉粥样硬化斑块的形成,其机制可能与丹酚酸B介导Piezo1调控MAPK/YAP轴相关。

    Abstract:

    Aim To investigate the protective effect and mechanism of salvianolic acid B (SalB) on oxidized low density lipoprotein (ox-LDL)-induced foam cell formation in atherosclerosis. Methods Bone marrow-derived macrophages (BMDM) were extracted from mice, and cells were induced with 50 mg/L ox-LDL. The Piezo1 channel agonist Yoda1 was added to observe the correlation with Piezo1. The drug group was treated with different concentrations of SalB. Results Foam cell formation was significantly increased in Yoda1+ox-LDL group(P<0.05). Compared with Yoda1+ox-LDL group, foam cell formation was significantly inhibited in SalB group (P<0.05). Compared with normal control group, the protein expressions of inflammatory factors were increased in ox-LDL group, and they were more obvious in Yoda1+ox-LDL group. The protein expression levels of inflammatory factors were significantly decreased in SalB group(P<0.05). In addition, the translocation of YAP protein into the nucleus was obvious in ox-LDL group, while it was more obvious in Yoda1+ox-LDL group, and the difference was significant (P<0.05). The translocation of YAP protein into the nucleus was significantly reduced in SalB group. The expressions of phosphorylated P38, ERK1/2 and JNK proteins were increased in ox-LDL group and Yoda1+ox-LDL group, while they were significantly decreased in SalB group, and the difference was statistically significant (P<0.05). Conclusion SalB inhibits foam cell formation and the protein expression levels of inflammatory factors induced by ox-LDL and Yoda1, thereby delaying the formation of atherosclerotic plaques. The mechanism may be that salvianolic acid B mediate Piezo1 to regulate MAPK/YAP axis.

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潘显梅,夏明峰,李静.丹酚酸B介导巨噬细胞Piezo1/MAPK/YAP轴对动脉粥样硬化的保护作用[J].中国动脉硬化杂志,2023,(1):17~23.

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  • 收稿日期:2022-04-30
  • 最后修改日期:2022-06-07
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  • 在线发布日期: 2022-12-26