Evodiamine inhibits PDGF‑BB‑induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress.
Evodiamine inhibits PDGF‑BB‑induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress.
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DOI：
10.3892/mmr.2016.5798
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发表时间：
2016-11
影响因子：
3.4
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Ge X;Chen SY;Liu M;Liang TM;Liu C
血管平滑肌细胞（VSMC）增殖是支架内再狭窄发生的关键事件。evolodiamine是一种从中药吴茱萸中提取的吲哚类生物碱，已被证明具有抑制肿瘤细胞增殖和保护心血管系统的作用。然而，evoldiine是否影响VSMC增殖仍有待阐明。因此，本研究探讨了evoldiine对大鼠VSMCs增殖的影响及其作用机制。细胞分别用evoldiine单独或联合血小板衍生生长因子- bb （PDGF-BB）刺激处理。结果发现，evoldiine抑制pdgf - bb诱导的VSMC增殖呈剂量依赖性，且不诱导细胞死亡。evolodiamine也延缓了细胞周期的进展，这可以通过抑制细胞周期促进蛋白和细胞周期蛋白依赖激酶的表达来证明。此外，伏伏二胺可减弱pdgf - bb诱导的丝裂原活化蛋白激酶p38和细胞外信号调节激酶1/2的磷酸化，但对Akt的磷酸化无影响。evolodiamine还抑制活性氧生成的增加，上调编码抗氧化酶基因的mRNA表达水平。这些发现为研究伏伏二胺的血管保护作用机制提供了重要的见解，并表明它可能是一种治疗血管闭塞性疾病的有效药物。
Vascular smooth muscle cell (VSMC) proliferation is a key event in the development of in-stent restenosis. Evodiamine is an indole alkaloid extracted from the Chinese medicine, evodia, and has been shown to inhibit tumor cell proliferation and protect the cardiovascular system. However, whether evodiamine affects VSMC proliferation remains to be elucidated. Therefore, the present study examined the effects and the mechanisms of action of evodiamine on the proliferation of rat VSMCs. The cells were treated with evodiamine alone or in combination with platelet-derived growth factor-BB (PDGF-BB) stimulation. It was found that evodiamine inhibited PDGF-BB-induced VSMC proliferation in a dose-dependent manner, without inducing cell death. Evodiamine also retarded cell cycle progression, evidenced by the suppression of the expression of cell cycle-promoting cyclin proteins and cyclin-dependent kinases. In addition, evodiamine attenuated the PDGF-BB-induced phosphorylation of mitogen-activated protein kinases p38 and extracellular signal-regulated kinases 1/2, however, it had no effect on the phosphorylation of Akt. Evodiamine also inhibited the increase of reactive oxygen species generation and upregulated the mRNA expression levels of genes encoding antioxidant enzymes. These findings provide important insights into the mechanisms underlying the vasoprotective actions of evodiamine and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease.