摘要
脉管的光滑的肌肉房间(VSMC ) 的增加的增长和移植是在动脉粥样硬化患者损害的开发的关键事件。Baicalin，导出植物的 flavonoid 混合物，以前被显示了通过多重小径在癌症房间导致 apoptosis 和生长抑制。然而，在 VSMC 增长和心血管的疾病的预防的规定的 baicalin 的潜在的角色仍然保持未经勘探。在这研究，我们证明有 baicalin 的那个预告的处理有一个剂量依赖者 PDGF-BB-stimulated VSMC 增长上的禁止的效果，与增殖的减小伴随了房间原子抗原(PCNA ) 表示。我们也证明导致 baicalin 的生长抑制在在 p27 的激活和增加在刺激 PDGF 的 VSMC 铺平的 cyclin E-CDK2 与减少被联系，它看起来是部分至少由 PDGF 受体尾的封锁调停了(PDGFR 尾) 发信号的细胞外的调整信号的 kinase 1/2 (ERK1/2 ) 。另外， baicalin 也被发现禁止 PDGF-BB 在 VSMC 导致的粘附分子表达式和房间移植。而且，使用一根动物颈动脉动脉的汽球损害模型，我们发现 baicalin 显著地禁止了 neointimal 增生。一起拿，我们的结果在导致生长揭示 baicalin 的新奇功能在汽球损害以后刺激 PDGF 的 VSMC 和压制的 neointimal 增生逮捕，并且建议内在的机制经由 PDGFR 尾 - 的封锁包含在 p27 累积的 cyclin E-CDK2 激活和增加的抑制 ERK1/2 发信号串联。
The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC pro- liferation, accompanied with the reduction of proliferating cell nuclear antigen （PCNA） expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF recep- tor [~ （PDGFR~）-extracellular signal-regulated kinase 1/2 （ERK1/2） signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFR^-ERK1/2 signaling cascade.
基金
We are grateful to Dr Guan KL （Moore＇s Cancer Center, La Jolla, CA, USA） for the gift of pCMV-MEKca. This study was supported by the National Natural Science Foundation of China （30770787 and 90919035）, the National Basic Research Program of China （2005CB523301）, and the International Cooperation in Science and Technology Projects （2006DFB32460） and the Hebei Province Natural Science Foundation （C2007000831）.
