NF-κB在炎症介质诱导的大鼠脑微血栓形成分子发病机制中的作用
he role of nuclear factor-kappaB in molecular mechanism of pathogenesis of rat brain microvascular thrombosis induced by inflammatory mediators
目的：以脂多糖（LPS）诱导下高表达组织因子（tissue factor，TF）的大鼠脑微血管内皮细胞（BMECs）为大鼠脑微血栓形成的细胞模型，探讨核因子κB（NF-κB）在炎症介质导致的脑微血栓形成中的作用。方法：制备大鼠脑微血管内皮细胞培养模型，分别用LPS刺激1/4、1/2、1、2、4、16h，以NF-κB特异性抑制剂PDTC（pyrrilidine dithiocarbamate）预处理组和空白对照组作为对照，采用流式细胞术特异性检测经BMECs膜表面TF定位表达丰度的变化，同时检测胞浆中TF的mRNA水平的变化，并进行计算机定量分析。 结果：TF在BMECs细胞中的表达与LPS作用呈现时间依赖关系，10μg/ml LPS刺激1/2h时TF表达开始升高，1h时达到最高值；100μmol/L PDTC预处理的BMECs在LPS刺激下，TF表达水平不升高。结论：LPS可以显著诱导BMECs中TF的表达，NF-κB是LPS诱导的BMECs TF表达的关键性转录调控分子，是炎症介质诱导的脑血栓形成发病分子机制中的重要因素。
Objective: To investigate the role of nuclear factor-kappaB (NF-κB) in tissue factor(TF) induction by inflammatory mediator lipopolysaccharide(LPS) in cultured rat brain microvascular endothelial cells(BMECs). Methods: The BMECs were isolated and cultured. Pyrrilidine dithiocarbamate (PDTC)，a special inhibitor of NF-κB pathway was used to preincubated on BMECs. TF expression of BMECs in response to LPS was examined by flow cytometry and RT-PCR. Results: TF expression showed a time-dependent manner of LPS. TF expression of BMECs began to rise after induced with LPS for 1/2h, reached top when induced for 1h;TF expression did not rise when BMECs were preincubated by 100μmol/L PDTC. Conclusion: NF-κB play a critical role in regulating TF transcription in LPS-induced BMECs and is a core factor in molecular mechanism of pathogenesis of cerebral thrombosis induced by inflammatory mediators .
王华芳、郑金娥、郭涛、胡豫、魏文宁
基础医学分子生物学神经病学、精神病学
脑微血管内皮细胞组织因子NF-κB炎症介质
brain microvascular endothelial cellstissue factorNF-κBinflammatory mediator
王华芳,郑金娥,郭涛,胡豫,魏文宁.NF-κB在炎症介质诱导的大鼠脑微血栓形成分子发病机制中的作用[EB/OL].(2009-04-02)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/200904-75.点此复制
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