Department of Pharmacology, Tzu Chi University , Hualien, Taiwan.
J Agric Food Chem. 2012 Jul 11;60(27):6832-8. doi: 10.1021/jf300771x. Epub 2012 Jun 26.
The development of restenosis involves migration and hyperproliferation of vascular smooth muscle cells (VSMCs). Platelet-derived growth factor (PDGF) is one of the major factors. Butein modulates inflammatory pathways and affects the proliferation and invasion of the tumor. We investigated the hypothesis that butein might prevent the restenosis process via a similar pathway. Our results demonstrated that butein inhibited PDGF-induced VSMC proliferation and migration as determined by BrdU proliferation and two-dimensional migration scratch assay. Butein also concentration-dependently repressed PDGF-induced phosphorylation of PDGF-receptor β, mitogen-activated protein kinases, phosphoinositide 3-kinase/Akt, and phopholipase Cγ/c-Src in VSMCs. In addition, in vivo results showed that butein attenuated neointima formation in balloon-injured rat carotid arteries. These results indicate that butein may inhibit PDGF-induced VSMC proliferation and migration, resulting in attenuation of neointima formation after percutaneous transluminal coronary angioplasty. Our study demonstrates for the first time that systemic administration of butein is able to reduce neointima formation after vascular injury.
再狭窄的发展涉及血管平滑肌细胞（VSMCs）的迁移和过度增殖。血小板衍生生长因子（PDGF）是主要因素之一。布替丁调节炎症途径，并影响肿瘤的增殖和侵袭。我们假设布替丁可能通过类似途径预防再狭窄过程。我们的结果表明，布替丁通过 BrdU 增殖和二维迁移划痕试验抑制 PDGF 诱导的 VSMC 增殖和迁移。布替丁还浓度依赖性地抑制 PDGF 诱导的 VSMCs 中 PDGF 受体 β、丝裂原活化蛋白激酶、磷酸肌醇 3-激酶/Akt 和磷酯酶 Cγ/c-Src 的磷酸化。此外，体内结果表明，布替丁减弱了球囊损伤大鼠颈动脉中的新生内膜形成。这些结果表明，布替丁可能抑制 PDGF 诱导的 VSMC 增殖和迁移，从而减轻经皮腔内冠状动脉成形术后的新生内膜形成。我们的研究首次表明，全身给予布替丁能够减少血管损伤后的新生内膜形成。
