白藜芦醇对损伤动脉再内皮化和内膜增生的影响
DOI:
作者:
作者单位:

作者简介:

通讯作者:

基金项目:

国家自然科学基金(30170365)项目


Effect of Resveratrol on Reendothelialization and Neointimal Formation in Intimal Injury Model
Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
    摘要:

    目的探讨白藜芦醇对大鼠主动脉内膜剥脱后内皮修复、内膜增生的影响及其潜在机制。方法54只雄性SD大鼠随机分为假手术组(n=9)、对照组(n=15)、小剂量[10 mg/(kg.d)]白藜芦醇组(n=15)和大剂量[50mg/(kg.d)]白藜芦醇组(n=15),术前2周至动物处死期间经灌胃器给药;术后1周、2周分别应用Ⅷ因子检测和伊文思蓝染色评价各组损伤血管内皮修复情况;术后2周、4周采用HE染色观察内膜增生情况;采用逆转录聚合酶链反应及免疫组织化学法评价术后1周4、周损伤血管的内皮型一氧化氮合酶mRNA和蛋白水平的表达;体外分离、培养大鼠外周血内皮祖细胞,并采用免疫组织化学法进行鉴定;通过倒置荧光显微镜计数双阳性细胞以评价各组术后1周的外周循环内皮祖细胞数量。结果10 mg/(kg.d)白藜芦醇明显促进术后1周及2周的内皮修复,而50mg/(kg.d)不能;10 mg/(kg.d)白藜芦醇显著抑制术后2周、4周的内膜增生,而50 mg/(kg.d)只能抑制术后4周的内膜增生,且效果不如前者;10 mg/(kg.d)白藜芦醇明显促进损伤血管的内皮型一氧化氮合酶mRNA水平和蛋白水平的表达,而50 mg/(kg.d)组与对照组无明显差异;与对照组相比,10 mg/(kg.d)白藜芦醇显著升高术后1周的外周血内皮祖细胞数量(32.46±6.52比21.58±3.69,p<0.05),而50 mg/(kg.d)白藜芦醇无明显差异(22.48±6.89比21.58±3.69,p<0.05)。结论小剂量白藜芦醇可上调损伤血管内膜的内皮型一氧化氮合酶表达、促进内皮祖细胞动员、加快内皮修复及抑制内膜增生;而大剂量白藜芦醇只能抑制术后4周的内膜增生。

    Abstract:

    Aim To investigate the effect of resveratrol on reendothelialization and intimal hyperplasia in balloon injured aorta of rat and its potential mechanism. Methods 54 healthy male Sprague-Dawley rats were randomly divided into 4 groups: sham operation group(n=9),placebo-treated group(n=15),small dose resveratrol [10 mg/(kg·d)] group(n=15) and large dose resveratrol [50 mg/(kg·d)] group(n=15).Rats were gavaged with resveratrol or placebo 2 weeks before balloon injury until sacrificed.At 1 and 2 weeks after endothelium denudation,Ⅷ factor immunohistochemical staining and Evans blue staining were used to measure the reendothelialized area.Neointimal formation was determined by HE staining at 2 and 4 weeks after operation.At 1 and 4 weeks after artery injury,endothelial nitric oxide synthase(eNOS) mRNA and protein expression were assayed by reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry,respectively. Endothelial progenitor cells(EPC) were isolated and cultured from rat peripheral blood,which were identified by immunohistochemistry,then the amount of EPC at 1 week after balloon injury were measured by counting DiI-acLDL/FITC-UEA-Ⅰdoublepositive cells in inverted fluorescence microscope. Results 10 mg/(kg·d) resveratrol significantly accelerated reendothelialization at 1 and 2 weeks after balloon injury,50 mg/(kg·d)could not.10 mg/(kg·d) resveratrol markedly inhibited neointimal formation at 2 and 4 weeks after operation,however,50 mg/(kg·d) only reduced neointimal formation at 4 weeks after operation,which was not as effective as previous one.The expressions of eNOS mRNA and protein were potently enhanced in 10 mg/(kg·d) resveratrol group,but not in 50 mg/(kg·d) group.10 mg/(kg·d) resveratrol also significantly increased the amount of EPC in rat peripheral blood at 1 week after operation compared with placebo-treated group(32.46±6.52 vs 21.58±3.69,p<0.05),while the results of 50 mg/kg group did not reach statistical difference(22.48±6.89 vs 21.58±3.69,p<0.05). Conclusions Small dose resveratrol could markedly increase the expression of eNOS,enhance the mobilization of EPC as well as accelerate reendothelialization and reduce neointimal formation compared with placebo-treated group.However,large dose resveratrol only attenuated the intimal hyperplasia at 4 weeks after operation.

    参考文献
    相似文献
    引证文献
引用本文

顾俊,王长谦,张大东,范华骅,何奔,王彬尧,黄定九.白藜芦醇对损伤动脉再内皮化和内膜增生的影响[J].中国动脉硬化杂志,2006,14(10):829~834.

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
历史
  • 收稿日期:2006-04-24
  • 最后修改日期:2006-10-08
  • 录用日期:
  • 在线发布日期: