小檗碱抑制氧化型低密度脂蛋白诱导的人脐静脉内皮细胞增殖及其分子机制  

Inhibitory effect of berberine on proliferation of human umbilical vein endothelial cells induced by oxidized low density lipoprotein and its molecular mechanism

作　　者：马春艳[1] 徐瑞霞[1] 姚雨宏 李小林[1] 郭远林[1] 张彦[1] 李莎[1] 李建军[1] 

机构地区：[1]中国医学科学院北京协和医学院国家心血管病中心阜外医院心血管疾病国家重点实验室血脂异常与心血管病诊治中心

出　　处：《中国动脉硬化杂志》2018年第2期144-151,共8页Chinese Journal of Arteriosclerosis

基　　金：北京协和医学院协和青年基金项目(3332016018);阜外医院科研人才支持计划项目(2012-FWXX02);首都卫生发展科研专项项目(2016-1-4035)

摘　　要：目的 探讨小檗碱对氧化型低密度脂蛋白（ox-LDL）诱导人脐静脉内皮细胞（HUVEC）增殖的抑制作用及其相关信号通路改变。方法 体外培养HUVEC,以ox-LDL刺激增殖并以不同浓度小檗碱干预,采用细胞计数试剂盒8与Ed U掺入实验检测小檗碱对HUVEC增殖的抑制作用,通过实时荧光定量PCR及Western blot分析相关基因和蛋白表达及信号通路变化。结果 小檗碱（1~50 mg/L）呈浓度依赖性显著抑制ox-LDL诱导的HUVEC增殖,并降低增殖细胞核抗原（PCNA）、核因子кB（NF-κB）、凝集素样氧化型低密度脂蛋白受体1（LOX-1）的表达;该作用与PI3K/Akt、ERK1/2及p38MAPK信号通路蛋白的磷酸化水平降低相关。结论 小檗碱通过下调PCNA、NF-κB与LOX-1表达从而抑制ox-LDL诱导的HUVEC增殖,PI3K/Akt、ERK1/2及p38MAPK信号通路参与其中。Aim To investigate the inhibitory effect of berberine on the proliferation of human umbilical vein endothelial cell （HUVEC） induced by oxidized low density lipoprotein （ox-LDL） and the changes of related signaling path- ways. Methods HUVEC was cultured in vitro, and the proliferation of HUVEC was stimulated by ox-LDL and inter- vened with berberine at different concentrations. The inhibitory effect of berberine on proliferation of HUVEC was detected by cell counting kit 8 and EdU incorporation experiment. The expressions of related genes and proteins and the changes of signaling pathway were analyzed by real-time quantitative PCR and Western blot. Results In a concentration depend- ent manner, berberine （ 1- 50 mg/L） significantly inhibited the HUVEC proliferation induced by ox-LDL, and reduced the expressions of proliferating cell nuclear antigen （PCNA）, nuclear factor KB （NF-KB） and lectin-like oxidized low density lipoprotein receptor-1 （LOX-1）. These effects were associated with decreased phosphorylation levels of PI3K/Akt, ERK1/2 and p38MAPK signaling pathways. Conclusion Berberine inhibits the proliferation of HUVEC induced by ox-LDL through the down-regulation of PCNA, NF-KB and LOX-1 expressions. PI3K/Akt, ERK1/2 and p38MAPK sig- naling pathways are involved in this process.

关 键 词：小檗碱 氧化型低密度脂蛋白 人脐静脉内皮细胞 细胞增殖 信号通路 

分 类 号：R363[医药卫生—病理学]