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新型植物抗氧化剂对动脉粥样硬化中血小板超氧化物生成和聚集的影响。

Effects of novel plant antioxidants on platelet superoxide production and aggregation in atherosclerosis.

作者信息

Ryszawa N, Kawczyńska-Drózdz A, Pryjma J, Czesnikiewicz-Guzik M, Adamek-Guzik T, Naruszewicz M, Korbut R, Guzik T J

机构信息

Department of Pharmacology, Jagiellonian University School of Medicine, Cracow, Poland.

出版信息

J Physiol Pharmacol. 2006 Dec;57(4):611-26.

Abstract

Superoxide anion is produced in human platelets predominantly by Nox2-dependent NADPH oxidases. In vitro experiments have shown that it might play a role in modulating platelet functions. The relationship between platelet superoxide production and aggregation remains poorly defined. Accordingly, we aimed to study superoxide production and aggregation in platelets from subjects with significant cardiovascular risk factors (hypertension, hypercholesterolemia, smoking and diabetes mellitus) and from control individuals. Moreover, we studied the effects of novel polyphenol-rich extracts of Aronia melanocarpa (chokeberry) berries on platelet function in vitro. Superoxide production was significantly increased in patients with cardiovascular risk profile when compared to controls, while platelet aggregation in response to either collagen or thrombin were borderline higher, and did not reach statistical significance. Interestingly, no relationship was observed between platelet aggregation ex vivo and platelet superoxide production in either of studied groups. No correlation was found between endothelial function (measured by FMD) and platelet aggregation ex vivo either. Polyphenol-rich extracts of A. melanocarpa berries caused a significant concentration dependent decrease in superoxide production only in patients with cardiovascular risk factors, while no effect was observed in the control group. A. melanocarpa extracts abolished the difference in superoxide production between risk factor patients and controls. A. melanocarpa extracts exerted significant concentration dependent anti-aggregatory effects in both studied groups, which indicated that these effects may be independent of it's ability to modulate superoxide production. The anti-aggregatory effects of chokeberry extracts were similar irrespective of aggregation inducing agent (collagen or thrombin). Moreover, they appear to be independent of platelet NO release as NOS inhibition by L-NAME did not lead to their abrogation.

摘要

超氧阴离子主要由人血小板中依赖Nox2的NADPH氧化酶产生。体外实验表明,它可能在调节血小板功能中发挥作用。血小板超氧产生与聚集之间的关系仍不清楚。因此,我们旨在研究有重大心血管危险因素(高血压、高胆固醇血症、吸烟和糖尿病)的受试者以及对照组个体血小板中的超氧产生和聚集情况。此外,我们研究了黑果腺肋花楸(野樱莓)浆果富含多酚的新型提取物对体外血小板功能的影响。与对照组相比,有心血管危险因素的患者超氧产生显著增加,而对胶原蛋白或凝血酶的血小板聚集略高,但未达到统计学意义。有趣的是,在任何一个研究组中,均未观察到体外血小板聚集与血小板超氧产生之间的关系。内皮功能(通过血流介导的血管舒张测定)与体外血小板聚集之间也未发现相关性。黑果腺肋花楸浆果富含多酚的提取物仅在有心血管危险因素的患者中导致超氧产生显著的浓度依赖性降低,而在对照组中未观察到影响。黑果腺肋花楸提取物消除了有危险因素患者与对照组之间超氧产生的差异。黑果腺肋花楸提取物在两个研究组中均发挥了显著的浓度依赖性抗聚集作用,这表明这些作用可能与其调节超氧产生的能力无关。无论聚集诱导剂是胶原蛋白还是凝血酶,野樱莓提取物的抗聚集作用均相似。此外,它们似乎与血小板一氧化氮释放无关,因为L-NAME抑制一氧化氮合酶并未导致其作用消失。

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