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  

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

作　　者：潘显梅 夏明峰 李静 PAN Xianmei;XIA Mingfeng;LI Jing(The First Affiliated Hospital,Guangzhou University of Chinese Medicine,Guangzhou,Guangdong 510405,China;Lingnan Medical Research Center,Guangzhou University of Chinese Medicine,Guangzhou,Guangdong 510405,China;Innovation Research Institute of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan,Shandong 250355,China)

机构地区：[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

出　　处：《中国动脉硬化杂志》2023年第1期17-23,共7页Chinese Journal of Arteriosclerosis

基　　金：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)。

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。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.

关 键 词：丹酚酸B Piezo1离子通道 骨髓来源巨噬细胞 动脉粥样硬化 

分 类 号：R363[医药卫生—病理学] R5[医药卫生—基础医学]