上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

瑞舒伐他汀抑制同型半胱氨酸诱导的内皮祖细胞凋亡涉及Nox4氧化应激途径

鲍晓梅1，郑宏超1，吴春芳2，陆国平2   

  1. 1.上海市徐汇区中心医院心内科， 上海 200031； 2.上海交通大学 医学院附属瑞金医院心内科， 上海 200025
  • 出版日期:2013-11-28 发布日期:2013-12-03
  • 作者简介:鲍晓梅（1972—）， 女， 副主任医师， 博士; 电子信箱: baoxiaomei_nt@sina.cn。
  • 基金资助:

    上海市自然科学基金项目（12ZR1429100）

Rosuvastatin inhibits homocysteine-induced oxidative stress and apoptosis in endothelial progenitor cells involving Nox4

BAO Xiao-mei1, ZHENG Hong-chao1, WU Chun-fang2, LU Guo-ping2   

  1. 1.Department of Cardiology, Xuhui District Central Hospital, Shanghai 200031, China; 2.Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2013-11-28 Published:2013-12-03
  • Supported by:

    Natural Science Foundation of Shanghai，12ZR1429100

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摘要：

目的 研究瑞舒伐他汀（Rosu）对同型半胱氨酸（Hcy）诱导的内皮祖细胞（EPCs）活性氧（ROS）产生以及凋亡的影响。方法 从外周血中分离EPCs与Hcy共孵育，或经Rosu、不同的应激信号通路抑制剂甲羟戊酸（100 μmol/L）、乙酰半胱氨酸（NAC，10 μmol/L）、NADPH氧化酶（Nox）抑制剂（DPI，10 μmol/L）、内皮一氧化氮合成酶抑制剂（LNMA，1 mmol/L）预培养后再加入Hcy共孵育。采用流式法检测细胞凋亡率，2,7-二氯荧光黄双乙酸盐法（H2DCF-DA）检测细胞内ROS水平，光泽精化学发光法检测Nox活性，RT-PCR检测Nox4 mRNA的表达。结果 Rosu显著抑制了Hcy诱导的ROS蓄积和EPCs凋亡，拮抗了Hcy诱导的Nox激活以及Nox4 mRNA表达。Nox4 siRNA转染EPCs可以产生相似的效果。结论 Rosu对EPCs的保护作用可能是通过Nox4途径抑制Hcy诱导的Nox激活、ROS蓄积和EPCs凋亡来实现。

关键词: 瑞舒伐他汀, 同型半胱氨酸, 凋亡, 活性氧, Nox4

Abstract:

Objective To study inhibition of rosuvastatin (Rosu) on homocysteine (Hcy)-induced reactive oxygen species (ROS) and apoptosis in endothelial progenitor cells (EPCs). Methods EPCs were isolated from peripheral blood and then incubated with Hcy, or pre-incubated with Rosu or with different stress signaling pathway inhibitors including mevalonate (100 μmol/L), acetyl-cysteine (NAC, 10 μmol/L), NADPH oxidase inhibitor (DPI, 10 μmol/L), and endothelial nitric oxide synthase inhibitor (LNMA, 1 mmol/L) before adding Hcy. Apoptosis rate was evaluated by fluorescence activated cell sorting (FACS) analysis. ROS levels were detected by 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFH-DA). NADPH oxidases were evaluated with lucigenin-enhanced chemiluminescence. Expression of Nox4 mRNA was measured by RT-PCR. Results Rosu remarkably inhibited Hcy-induced ROS accumulation and apoptosis of EPCs, and antagonized Hcy-induced activation of NADPH oxidase and Nox4 mRNA expression. Nox4 siRNA transfected EPCs with a similar effect. Conclusion The protective effect of Rosu on EPCs possibly involves inhibition of Hcy-induced activation of Nox, ROS accumulation, and apoptosis of EPCs through Nox4 dependent mechanisms.

Key words: rosuvastatin, homocysteine, apoptosis, reactive oxygen species, Nox4