Emodin as a selective proliferative inhibitor of vascular smooth muscle cells versus endothelial cells suppress arterial intima formation
Emodin as a selective proliferative inhibitor of vascular smooth muscle cells versus endothelial cells suppress arterial intima formation
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大黄素作为血管平滑肌细胞与内皮细胞的选择性增殖抑制剂抑制动脉内膜形成
DOI：
10.1016/j.lfs.2018.05.042
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发表时间：
2018-08
期刊：
影响因子：
6.1
通讯作者：
Dong Nianguo
中科院分区：
文献类型：
--
作者：
Xu Kang;Al-ani Mohanad Kh.;Wang Chunli;Qiu Xuefeng;Chi Qingjia;Zhu Peng;Dong Nianguo
大黄素是一种著名的天然蒽醌类化合物，具有抑制血管平滑肌细胞增殖的作用。但大黄素对VSMCs和血管内皮细胞（VECs）的抗增殖作用在很大程度上仍然未知。本研究旨在比较大黄素对人血管平滑肌细胞和血管内皮细胞增殖的影响。采用MTS、EdU、FACS、qRT-PCR和线粒体荧光探针等方法分别检测细胞活力、DNA合成速率、细胞周期、增殖基因表达水平和线粒体活性。采用颈动脉球囊损伤模型，观察大黄素对颈动脉内膜增生及再内皮化的影响。大黄素（0.05 ~ 5 μM）对体外培养的hVSMCs增殖的抑制作用明显高于hVECs。大黄素浓度范围（2.5和5 μM）的条件培养基降低了hVSMC和hVECs细胞中CDK 1、Ki 67和E2 F-1基因的表达，沿着线粒体活性的抑制，而前者仍然高度敏感。腹腔注射大黄素（10 mg/kg）2周，可明显减轻在体损伤动脉内皮剥脱诱导的-IH形成和有限的再内皮化。大黄素在体外可优先抑制hVSMCs的增殖，但对hVECs无明显抑制作用，在大鼠动脉内皮剥脱模型中，大黄素对hVECs再内皮化的影响有限。结论大黄素是一种有效预防血管再狭窄的有效药物。
A well-known natural anthraquinone “Emodin”, has been proven to inhibit the proliferation of vascular smooth muscle cells (VSMCs). But the anti-proliferative effects of emodin on both VSMCs versus vascular endothelial cells (VECs) are still largely unknown. Herein, a comparative study for the evaluation of anti-proliferation effects of emodin on human VSMCs and VECs was designed. Various methodologies including MTS, EdU assay, FACS analysis, qRT-PCR and mitochondrial fluorescent probes were used for detecting cell viabilities, DNA synthesis rate, cell cycle, proliferation genes expression levels and mitochondrial activities, respectively. In addition, carotid arteries balloon injury was performed to evaluate the effects of emodin on intima hyperplasia (IH) and re-endothelialization. The emodin showed a dose-dependent (0.05 to 5 μM) inhibition of hVSMCs proliferation was quiet higher than hVECs in vitro. Conditioned culture media with a range of emodin concentrations (2.5, and 5 μM) reduced CDK1, Ki67, and E2F-1 gene expression, along with inhibition of mitochondrial activities in both hVSMCs and hVECs cells, while former remained highly sensitive. Emodin (10 mg/kg) was injected intraperitoneally for 2 weeks, and had obvious alleviation in an endothelial denudation induced-IH formation and limited interfere-endothelialization in injured arteries in vivo. Emodin preferentially inhibited hVSMCs proliferation but not the hVECs in vitro and had limited influence on the re-endothelialization of later in a rat artery endothelial denudation model. It is concluded that emodin will provide a promising approach for efficient prevention of blood vessel restenosis.
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影响因子：
3.7
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通讯作者：
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