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β-榄香烯对损伤动脉内皮细胞的保护作用及其对血管内膜增生的抑制作用。

Protection of endothelial cells, inhibition of neointimal hyperplasia by β-elemene in an injured artery.

机构信息

Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Chongqing Engineering Lab. in Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China.

出版信息

Cardiovasc Drugs Ther. 2011 Jun;25(3):233-42. doi: 10.1007/s10557-011-6305-9.

DOI:10.1007/s10557-011-6305-9
PMID:21607546
Abstract

AIMS

It is generally accepted that the oxidative stress and the proliferative activity of vascular smooth muscle cells (VSMCs) contribute to the pathogenesis of neointimal hyperplasia after vascular injury. Although β-elemene (β-1-methyl-1-vinyl-2, 4-diisopropenyl-cyclohexane) has been used as an antitumour drug, its therapeutic effect on vascular diseases has not yet been determined. In this study, we investigated whether β-elemene could inhibit oxidative damage of vascular endothelial cells, suppress VSMCs growth and prevent neointimal hyperplasia.

METHODS AND RESULTS

β-elemene can increase the survival rate of human umbilical vein endothelial cells in vitro. By measuring the malondialdehyde content, total antioxidant capacity, superoxide dismutase activity, catalase activity, glutathione peroxidase activity and nitric oxide levels, we assessed the protective effect of β-elemene in the vascular endothelium model against oxidant-induced injury. Μoreover, β-elemene inhibited cell proliferation and induced apoptosis in cultured VSMCs. In a flow culture system, β-elemene reduced the migration distance of VSMCs. By transwell migration assay, β-elemene was found to reduce the migration cell number of VSMCs, but not affect the HUVECs migration. In a rat carotid artery balloon injury model, administration of β-elemene significantly reduced the ratio of intimal area to medial area and neointima formation.

CONCLUSIONS

Our results indicate that β-elemene is effective in protecting the endothelial cells from injury induced by hydrogen peroxide in vitro, inhibiting smooth muscle cell proliferation/migration and inhibiting neointima formation in vivo after vascular injury.

摘要

目的

氧化应激和血管平滑肌细胞(VSMC)的增殖活性被认为是血管损伤后新生内膜增生的发病机制。虽然β-榄香烯(β-1-甲基-1-乙烯基-2,4-二异丙烯基环己烷)已被用作抗肿瘤药物,但它对血管疾病的治疗效果尚未确定。在这项研究中,我们研究了β-榄香烯是否可以抑制血管内皮细胞的氧化损伤,抑制 VSMC 的生长并预防新生内膜增生。

方法和结果

β-榄香烯可以提高人脐静脉内皮细胞在体外的存活率。通过测量丙二醛含量、总抗氧化能力、超氧化物歧化酶活性、过氧化氢酶活性、谷胱甘肽过氧化物酶活性和一氧化氮水平,我们评估了β-榄香烯在血管内皮细胞模型中对抗氧化剂诱导损伤的保护作用。此外,β-榄香烯抑制培养的 VSMC 的增殖并诱导其凋亡。在流动培养系统中,β-榄香烯减少了 VSMC 的迁移距离。通过 Transwell 迁移实验,发现β-榄香烯减少了 VSMC 的迁移细胞数量,但不影响 HUVECs 的迁移。在大鼠颈动脉球囊损伤模型中,β-榄香烯给药显著降低了内膜面积与中膜面积的比值和新生内膜的形成。

结论

我们的结果表明,β-榄香烯在体外有效保护内皮细胞免受过氧化氢诱导的损伤,抑制血管损伤后平滑肌细胞的增殖/迁移,并抑制新生内膜的形成。

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