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NOX2 介导的吸烟者动脉功能障碍:黑巧克力的急性作用。

NOX2-mediated arterial dysfunction in smokers: acute effect of dark chocolate.

机构信息

I Clinica Medica, Viale del Policlinico 155, Roma 00161, Italy.

出版信息

Heart. 2011 Nov;97(21):1776-81. doi: 10.1136/heartjnl-2011-300304. Epub 2011 Jul 31.

DOI:10.1136/heartjnl-2011-300304
PMID:21807659
Abstract

BACKGROUND

Cocoa seems to exert artery dilatation via oxidative stress inhibition but the mechanism is still unclear.

OBJECTIVES

To investigate whether in smokers, dark chocolate elicits artery dilatation via down-regulation of NOX2, the catalytic core of NADPH oxidase.

METHODS

Flow-mediated dilatation (FMD), oxidative stress (as assessed by urinary isoprostanes excretion), nitric oxide generation (as assessed by serum levels of nitrite/nitrate (NOx)), NOX2 activity (as assessed by blood levels of soluble NOX2 derived peptide (sNOX2-dp)) and serum epicatechin were studied in 20 smokers and 20 healthy subjects (HS) in a crossover, single-blind study. Patients were randomly allocated to 40 g dark chocolate (>85% cocoa) or 40 g of milk chocolate (≤35% cocoa). FMD, urinary isoprostanes, NOx and sNOX2-dp were assessed at baseline and 2 h after chocolate ingestion.

RESULTS

Smokers had lower FMD and NOx and higher sNOX2-dp compared to HS. After dark chocolate intake, urinary isoprostanes and sNOX2-dp significantly decreased and FMD and NOx significantly increased in smokers but not in HS. No changes of the above variables were observed after milk chocolate intake. Multiple linear regression analysis showed that in smokers the only independent predictive variable associated with a change in FMD was a change in sNOX2-dp. Serum epicatechin increased in either group only after dark chocolate intake, reaching values higher than 0.1 μM. Platelets from smokers (n=5), but not from HS (n=5), showed lower p47(phox) translocation to platelet membrane and higher NOx when incubated with 0.1-10 μM epicatechin.

CONCLUSION

Results suggest that in smokers, cocoa enhances artery dilatation by lowering of NOX2 activation.

摘要

背景

可可似乎通过抑制氧化应激来发挥血管舒张作用,但具体机制尚不清楚。

目的

研究在吸烟者中,黑巧克力是否通过下调 NADPH 氧化酶的催化核心 NOX2 来引起血管舒张。

方法

在一项交叉、单盲研究中,我们研究了 20 名吸烟者和 20 名健康受试者(HS)的血流介导的舒张功能(FMD)、氧化应激(通过尿中异前列腺素排泄评估)、一氧化氮生成(通过血清中硝酸盐/亚硝酸盐(NOx)水平评估)、NOX2 活性(通过血液中可溶性 NOX2 衍生肽(sNOX2-dp)水平评估)和血清表儿茶素。患者随机分为 40g 黑巧克力(可可含量>85%)或 40g 牛奶巧克力(可可含量≤35%)组。在巧克力摄入前和摄入后 2 小时评估 FMD、尿异前列腺素、NOx 和 sNOX2-dp。

结果

与 HS 相比,吸烟者的 FMD 和 NOx 较低,sNOX2-dp 较高。摄入黑巧克力后,吸烟者的尿异前列腺素和 sNOX2-dp 显著降低,FMD 和 NOx 显著升高,但 HS 无此变化。摄入牛奶巧克力后,上述变量均无变化。多元线性回归分析显示,在吸烟者中,唯一与 FMD 变化相关的独立预测变量是 sNOX2-dp 的变化。只有在摄入黑巧克力后,两组的血清表儿茶素均增加,达到 0.1 μM 以上。与 HS (n=5)相比,仅从吸烟者(n=5)血小板中观察到 p47(phox)向血小板膜的转位减少和 NOx 增加,当用 0.1-10 μM 表儿茶素孵育时。

结论

结果表明,在吸烟者中,可可通过降低 NOX2 激活来增强血管舒张。

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