Cordycepin Attenuates Neointimal Formation by Inhibiting Reactive Oxygen Species-Mediated Responses in Vascular Smooth Muscle Cells in Rats
Cordycepin Attenuates Neointimal Formation by Inhibiting Reactive Oxygen Species-Mediated Responses in Vascular Smooth Muscle Cells in Rats
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DOI：
10.1254/jphs.08308fp
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发表时间：
2009-03-01
影响因子：
3.5
通讯作者：
Kim, Bokyung
中科院分区：
文献类型：
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作者：
Won, Kyung-Jong;Lee, Su-Chan;Kim, Bokyung
我们确定了蛹虫草的主要生物活性成分冬虫夏草素对大鼠主动脉平滑肌细胞（RASMCs）和油血管疾病（特别是新内膜形成）反应的作用机制。冬虫夏草素以剂量依赖的方式抑制血小板衍生生长因子- bb （PDGF-BB）诱导的RASMCs迁移和增殖。然而，用一氧化氮合酶（NOS）抑制剂n -omega-硝基- l-精氨酸甲酯和a (1)/ a(2)腺苷受体拮抗剂1,3-二丙基-8-硫代巯基黄嘌呤（DPSPX）预处理虫草素，可以消除虫草素的抑制作用。虫草素抑制PDGF-BB刺激的RASMCs中p38丝裂原活化蛋白激酶（p38 MAPK）和热休克蛋白27 （Hsp27）的磷酸化，但对细胞外信号调节激酶（ER-K） 1/2的磷酸化无抑制作用。虫草素可消除PDGF-BB诱导的活性氧（ROS）、O-2（-）和H2O2的产生。冬虫夏草素对PDGF-BB的主动脉环芽出有抑制作用。虫草素可显著减轻球囊损伤引起的体内新生内膜形成。这些结果表明，虫草素可能通过干扰腺苷受体介导的NOS通路，对pdgf - bb诱导的迁移和增殖产生抑制作用，从而减弱新生内膜的形成。总之，虫草素可能是一种有效的，有前途的抗动脉粥样硬化剂。
We determined the action mechanism of cordycepin, a major bioactive component of Cordyceps militaris, on responses of rat aortic smooth muscle cells (RASMCs) and oil vascular disorders, especially neointimal formation. Cordycepin inhibited plate let-derived growth factor-BB (PDGF-BB)-induced RASMCs migration and proliferation in a dose-dependent manner. However, pre-treatment with N-omega-nitro-L-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor, and 1,3-dipropyl-8-sulpliopheilylxanthine (DPSPX), an A(1)/A(2) adenosine-receptor antagonist, abolished the inhibitory role of cordycepin. Cordycepin suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and heat shock protein 27 (Hsp27), but not that of extracellular signal-regulated kinase (ER-K) 1/2 in RASMCs stimulated by PDGF-BB. The production of reactive oxygen species (ROS), O-2(-) and H2O2, induced by PDGF-BB was abolished by the treatment of cordycepin. Moreover, the sprout outgrowth of aortic rings by PDGF-BB was inhibited by cordycepin. In vivo neointimal formation evoked by balloon-injury was significantly attenuated by the administration of cordycepin. These results demonstrate that cordycepin may exert inhibitory effects on PDGF-BB-induced migration and proliferation via interfering with adenosine receptor-mediated NOS pathways, thus resulting in the attenuation of neointima formation. In conclusion, cordycepin may be a potent, promising anti-atherosclerosis agent.