Atractylenolide I restores HO-1 expression and inhibits Ox-LDL-induced VSMCs proliferation, migration and inflammatory responses in vitro
Atractylenolide I restores HO-1 expression and inhibits Ox-LDL-induced VSMCs proliferation, migration and inflammatory responses in vitro
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DOI：
10.1016/j.yexcr.2017.02.040
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发表时间：
2017-04-01
影响因子：
3.7
通讯作者：
Niu, Xiaofeng
中科院分区：
文献类型：
--
作者：
Li, Weifeng;Zhi, Wenbing;Niu, Xiaofeng
动脉粥样硬化的发病机制以血管平滑肌细胞（VSMCs）的增殖和迁移以及炎性病变为特征。本研究旨在探讨奥曲肽I（AO-I）对氧化修饰低密度脂蛋白（Ox-LDL）诱导的平滑肌细胞炎症、增殖和迁移的影响。本研究发现，雷公藤甲素能剂量依赖性地抑制Ox-LDL诱导的VSMCs增殖和迁移，并能降低VSMCs炎症因子的产生和单核细胞趋化蛋白-1（MCP-1）的表达。本研究还发现AO-I显著抑制p38-MAPK和NF-κ 3的活化。更重要的是，特定的血红素加氧酶-1（HO-1）抑制剂锌原卟啉（ZnPP）IX部分消除了阿托伐他汀I对OxLDL诱导的VSMCs的有益作用。此外，雷公藤多甙I阻断Ox-LDL诱导的巨噬细胞泡沫细胞形成。总之，AO-I抑制VSMCs增殖和迁移、脂质过氧化及随后的炎症反应的作用可能是其抗动脉粥样硬化的作用机制之一。
Pathogenesis of atherosclerosis is characterized by the proliferation and migration of vascular smooth muscle cells (VSMCs) and inflammatory lesions. The aim of this study is to elucidate the effect of atractylenolide I (AO-I) on smooth muscle cell inflammation, proliferation and migration induced by oxidized modified low density lipoprotein (Ox-LDL). Here, We found that atractylenolide I inhibited Ox-LDL-induced VSMCs proliferation and migration in a dose-dependent manner, and decreased the production of inflammatory cytokines and the expression of monocyte chemoattractant protein-1 (MCP-1) in VSMCs. The study also identified that AO-I prominently inhibited p38-MAPK and NF-kappa 3 activation. More importantly, the specific heme oxygenase-1(HO-1) inhibitor zinc protoporphyrin (ZnPP) IX partially abolished the beneficial effects of atractylenolide I on OxLDL-induced VSMCs. Furthermore, atractylenolide I blocked the foam cell formation in macrophages induced by Ox-LDL. In summary, inhibitory roles of AO-I in VSMCs proliferation and migration, lipid peroxidation and subsequent inflammatory responses might contribute to the anti-atherosclerotic property of AO-I.