基础医学与临床 ›› 2017, Vol. 37 ›› Issue (5): 636-642.

• 研究论文 • 上一篇    下一篇

姜黄素抑制oxLDL诱导HUVECs凋亡

王德伟,张冬颖,曹黎,刘剑   

  1. 重庆医科大学附属第一医院
  • 收稿日期:2016-12-20 修回日期:2017-01-17 出版日期:2017-05-05 发布日期:2017-04-19
  • 通讯作者: 刘剑 E-mail:liujian819@126.com
  • 基金资助:
    重庆市卫生局中医药科技资助项目

Curcumin inhibits the apoptosis of HUVECs induced by oxidized low density lipoprotein

  • Received:2016-12-20 Revised:2017-01-17 Online:2017-05-05 Published:2017-04-19
  • Supported by:
    Chongqing Municipal Health Bureau Chinese medicine science and technology funding project

摘要: 目的 研究姜黄素对氧化低密度脂蛋白(oxLDL)诱导的人脐静脉内皮细胞(HUVECs)凋亡的保护作用及其可能机制。方法 体外培养HUVECs,实验分为:对照组、oxLDL组、oxLDL加内质网应激(ERS)抑制剂PBA组、姜黄素组、oxLDL加姜黄素组和oxLDL加姜黄素加PI3K抑制剂LY294002组。CCK-8法检测细胞存活率;流式细胞仪检测细胞凋亡;激光共聚焦显微镜观察活化转录因子6(ATF6)转位;Western bolt检测ERS相关蛋白:糖调节蛋白78(GRP78)、RNA样内质网激酶(PERK)和肌醇激酶-1(IRE-1)以及相关通路蛋白:LOX-1、AKT和p-AKT的表达。结果 与对照组相比,oxLDL可增加细胞凋亡,提高ERS相关蛋白的表达(P<0.01),促使ATF6向核内转位,以及提高LOX-1(P<0.01)和降低p-AKT的表达(P<0.01);与oxLDL组相比,PBA可抑制oxLDL诱导的细胞凋亡(P<0.01),姜黄素可抑制oxLDL诱导的ERS相关蛋白和LOX-1的表达(P<0.01),ATF6的核转位,内皮细胞的凋亡(P<0.01),同时它还可提高oxLDL引起的p-AKT表达下调(P<0.01);LY294002可部分削弱姜黄素抑制oxLDL诱导ERS相关蛋白表达的作用(P<0.05)。结论 姜黄素可降低oxLDL诱导HUVECs的凋亡,其可能机制是通过抑制LOX-1的表达和激活AKT通路减轻细胞ERS来实现的。

关键词: 姜黄素, oxLDL, ERS, HUVECs, 凋亡

Abstract: Objective To investigate the protective effect of curcumin on apoptosis of human umbilical vein endothelial cells (HUVECs) induced by oxidized low density lipoprotein (ox-LDL) and its possiblemechanism.Methods Cultivated HUVECs were divided into six groups: control group, oxLDLgroup,oxLDL plus endoplasmic reticulum stress(ERS) inhibitor PBA group,curcumin group, oxLDLpluscurcumingroup,oxLDL plus curcumin plus PI3K inhibitor LY294002 group.Cell viabilities were evaluated by CCK-8 assays .The proportions of apoptotic cells were assessed by flow cytometry .The translocation of activating transcription factor 6 (ATF6) abserved by laser confocal microscopy.Western blot was used to determine the expression of the ERS associated proteins:glucose-regulated protein 78( GRP78)、protein kinase-like ER kinase(PERK) 、inositol-requiring kinase1(IRE-1) and the related pathways protein:LOX-1、AKT and phophorylated AKT. Results Compared with control group,increased the proportions of apoptotic cells(P<0.01),enhanced the expressions of ERS related proteins(P<0.01),promoted the transfer of ATF6 into the nucleus,as well as increased the expression of LOX-1(P<0.01)and decreased the expression of p-AKT(P<0.01) in the oxLDLgroup;Compared with oxLDLgroup,PBAinhibited oxLDL-induced HUVECs apoptosis(P<0.01),curcumininhibited oxLDL-induced the expression of ERS associated protein and LOX-1(P<0.01), the nuclear translocation of ATF6, the apoptosis of HUVECs (P<0.01), and it also increased oxLDL-induced down-regulation of p-AKT expression (P<0.01); LY294002partially attenuated the inhibitory effect of curcumin on ERstress-related protein expression induced by oxLDL(P<0.05). Conclusions Curcumin can reduce oxLDL induced apoptosis of HUVECs, its mechanism may be through the inhibition of LOX-1 expression and activation of AKT pathway to reduce ERS in cell.

Key words: curcumin, oxLDL, endoplasmic reticulum stress, HUVECs, apoptosis

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