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白介素-1β增加血腦腫瘤屏障通透性的作用機(jī)制

發(fā)布時(shí)間:2018-02-02 11:06

  本文關(guān)鍵詞: 血管內(nèi)皮生長(zhǎng)因子 白介素-β 血腫瘤屏障 caveo-lin- 膠質(zhì)瘤 質(zhì)膜微囊小凹 出處:《中國(guó)藥理學(xué)通報(bào)》2016年01期  論文類型:期刊論文


【摘要】:目的研究白介素-1β(interleukin-1β,IL-1β)對(duì)膠質(zhì)瘤細(xì)胞內(nèi)血管內(nèi)皮生長(zhǎng)因子(vascular endothelial growth factor,VEGF)、腦血管內(nèi)皮細(xì)胞內(nèi)質(zhì)膜微囊結(jié)構(gòu)蛋白caveolin-1表達(dá)和質(zhì)膜微囊小凹的影響,初步探討IL-1β開放血腫瘤屏障的可能機(jī)制。方法利用Transwell制備體外血腫瘤屏障模型。Western blot法動(dòng)態(tài)監(jiān)測(cè)IL-1β對(duì)膠質(zhì)瘤細(xì)胞內(nèi)VEGF、腦血管內(nèi)皮細(xì)胞內(nèi)caveolin-1蛋白表達(dá)水平的影響。透射電鏡觀察腦血管內(nèi)皮細(xì)胞內(nèi)質(zhì)膜微囊小凹的數(shù)量,熒光素鈉滲出實(shí)驗(yàn)評(píng)估IL-1β對(duì)血腫瘤屏障通透性的影響。結(jié)果成功建立了體外血腫瘤屏障模型。當(dāng)IL-1β作用于體外血腫瘤屏障模型后,VEGF蛋白的表達(dá)量增加,于60min時(shí)達(dá)到峰值,至120min時(shí)恢復(fù)到初始狀態(tài)。體外血腫瘤屏障通透性亦于IL-1β作用60min時(shí)最大。另外,我們的研究結(jié)果還發(fā)現(xiàn),IL-1β作用于血腫瘤屏障模型60min時(shí),腦微血管內(nèi)皮細(xì)胞中質(zhì)膜微囊結(jié)構(gòu)蛋白caveolin-1的蛋白表達(dá)水平及質(zhì)膜微囊小凹的數(shù)量達(dá)到峰值,其后減少,并于120min時(shí)恢復(fù)到未給藥狀態(tài)。結(jié)論 IL-1β增加了血腫瘤屏障的通透性,此作用可能與IL-1β通過(guò)VEGF/caveolin-1途徑增加了質(zhì)膜微囊小凹數(shù)量有關(guān)。
[Abstract]:Objective to study interleukin-1 尾 interleukin-1 尾. IL-1 尾 was used to treat vascular endothelial growth factor (VEGF) in glioma cells. The expression of plasma membrane microcapsule structural protein (caveolin-1) in cerebrovascular endothelial cells and the effect of plasma membrane microcapsule fovea. To explore the possible mechanism of IL-1 尾 opening blood tumor barrier. Methods the model of blood tumor barrier in vitro was established by Transwell. VEGF in glioma cells was dynamically monitored by IL-1 尾 by blot. The expression of caveolin-1 protein in cerebrovascular endothelial cells was observed by transmission electron microscope. The effect of IL-1 尾 on blood tumor barrier permeability was evaluated by fluorescein sodium exudation test. Results the blood tumor barrier model in vitro was successfully established. When IL-1 尾 acted on the blood tumor barrier model in vitro. The expression of VEGF protein increased and reached its peak at 60min. The blood tumor barrier permeability in vitro was also maximum at 60min after exposure to IL-1 尾. The model of blood-tumor barrier was treated with IL-1 尾 for 60min. The expression level of plasma membrane microcapsule structure protein (caveolin-1) and the number of plasma membrane microcapsule fovea reached the peak in the cerebral microvascular endothelial cells, and then decreased. Conclusion IL-1 尾 can increase the permeability of blood tumor barrier. This effect may be related to the increase of the number of microvesicles in plasma membrane by IL-1 尾 via VEGF/caveolin-1 pathway.
【作者單位】: 華北理工大學(xué)基礎(chǔ)醫(yī)學(xué)院;
【基金】:國(guó)家自然科學(xué)基金資助項(xiàng)目(No 81101912) 河北省中醫(yī)藥管理局中醫(yī)藥類科研項(xiàng)目(No 2014195) 河北省衛(wèi)生廳科學(xué)研究基金項(xiàng)目(No 20150491) 河北省科技計(jì)劃項(xiàng)目(No 152777189)
【分類號(hào)】:R322.81
【正文快照】: 神經(jīng)膠質(zhì)瘤簡(jiǎn)稱膠質(zhì)瘤,是起源于神經(jīng)膠質(zhì)細(xì)胞的一種惡性腦腫瘤。目前臨床上對(duì)神經(jīng)膠質(zhì)瘤的治療大多主張綜合治療,即臨床手術(shù)后配合放化療等,以此來(lái)延長(zhǎng)患者的生存時(shí)間,遏制其復(fù)發(fā)[1-2]。在臨床膠質(zhì)瘤的治療過(guò)程中,由于血腫瘤屏障的存在,化療藥物無(wú)法直接進(jìn)入病灶,即使有少量進(jìn)

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