| Summary: | 碩士 === 慈濟大學 === 藥理暨毒理學研究所 === 99 === Restenosis is the major drawback after percutaneous transluminal coronary angioplasty (PTCA). The development of restenosis process involves migration and hyperproliferation of vascular smooth muscle cells (VSMCs). Platelet-derived growth factor (PDGF) activates VSMCs through Akt and ERK 1/2 signaling pathway. 3,4,2’,4’-Tetrahydroxychalcone (butein) modulates inflammatory pathways and affects the proliferation and invasion of the tumor through phosphorylation of Akt and ERK 1/2 inhibition. In this study, we investigated the effects of butein on VSMCs proliferation, migration in vitro and neointima formation in rat balloon injury model in vivo. Our results demonstrated that butein (10 μM) could inhibit PDGF-induced VSMCs proliferation and migration as determined by BrdU proliferation and two-dimensional migration scratch assay. We confirmed these inhibitions of butein were not due to cytotoxicity according to LDH release assay. Furthermore, our data showed that butein dose-dependently repressed PDGF-induced phosphorylation of PDGF-receptor β, MAPKs, PI3K/Akt, and PLCγ/c-Src in VSMCs. In addition, in vivo results showed that butein attenuated neointima formation in balloon-injured rat carotid arteries at a dose of 1.37 mg/kg/day, intraperitoneally. These results indicate that butein may inhibit PDGF-induced VSMC proliferation and migration, resulting in attenuating neointima formation after PTCA.
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