王婷,徐元珊,李红梅

• 1:北京中医药大学生命科学学院

摘要(Abstract)：

目的 探索紫杉醇-重组水蛭素介入涂层复合物（LFN）调控Notch-1和NF-κB通路间交互作用关键位点抗再狭窄的微观机制。方法 利用网络药理学技术初筛LFN调控双信号通路交互作用的预测靶点，构建LPS+Jagged-1诱导人冠状动脉平滑肌细胞（HCASMCs）增殖迁移模型，通过敲减或过表达双通路间枢纽基因，明确其交互作用与HCASMCs增殖迁移的相关性。在此基础上，对LFN初筛靶点进行精筛，进而在HCASMCs模型上予以LFN干预，从LFN双向调控Notch-1和NF-κB通路切入，深入阐释LFN防治介入术后再狭窄的细胞学机制。结果 网络药理学筛选结果表明，LFN对再狭窄的调控包含多种生物学模块和过程。联合LPS和Jagged-1以1μg/ml的浓度24 h持续刺激HCASMCs可诱导建立双通路活化细胞模型。与模型组比较，最佳浓度下的LFN(1μmol/L的紫杉醇配比0.2 mg/ml比伐芦定)对造模活化后的HCASMCs迁移和增殖变化具有显著抑制作用，可下调HCASMCs中NF-κB和Notch-1基因表达、上调IκBα基因表达，降低NICD、VEGF、MMP2、MMP9和Bcl-xL基因表达，同时下调OPN、PCNA、Notch-1和NF-κB（细胞核）蛋白表达、上调NF-κB（细胞质）蛋白表达（P<0.05）。其中，Notch-1与NICD表达的变化可直接影响LFN的作用效果。结论 LFN的抗再狭窄效应是通过调节Notch-1和NF-κB双通路间交互作用、阻断HCASMCs从收缩型向分泌型转变而实现。

关键词(KeyWords)： 紫杉醇-重组水蛭素介入涂层;抗再狭窄;NF-κB和Notch-1通路;细胞学机制;微观调控

Abstract:

Keywords:

基金项目(Foundation): 北京市自然科学基金面上项目（7222279）

作者(Author): 王婷,徐元珊,李红梅

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