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β-欖香烯對吉非替尼在體外血腦屏障模型中轉(zhuǎn)運的影響

發(fā)布時間:2018-02-26 07:36

  本文關(guān)鍵詞: β-欖香烯 吉非替尼 血腦屏障 P-糖蛋白 非小細胞肺癌 出處:《中國人民解放軍醫(yī)學(xué)院》2014年碩士論文 論文類型:學(xué)位論文


【摘要】:目的:建立簡單的體外血腦屏障滲透模型研究β-欖香烯是否通過抑制P-糖蛋白影響吉非替尼的跨膜轉(zhuǎn)運。 方法:在transwell裝置中原代培養(yǎng)的大鼠腦微血管內(nèi)皮細胞和星型膠質(zhì)細胞建立共培養(yǎng)去模擬體內(nèi)血腦屏障。用細胞電阻儀和熒光素鈉來監(jiān)測屏障模型的完整性。運用羅丹明-123滲透系數(shù)大小來衡量P-糖蛋白功能變化。液質(zhì)聯(lián)用方法測量吉非替尼的跨膜轉(zhuǎn)運量并計算表觀滲透系數(shù). 結(jié)果:測得的熒光素鈉Pe為4.90±1.31×10-6cms-1,跨膜電阻值為317.56±19.34cm2,,揭示成功建立屏障模型。在和欖香烯合用時,吉非替尼透過模型增加2.3倍。機制上,欖香烯抑制P-糖蛋白的轉(zhuǎn)運增加了羅丹明123的透過血腦屏障模型量,揭示了欖香烯和吉非替尼通過P-糖蛋白介導(dǎo)產(chǎn)生了相互作用。 結(jié)論:欖香烯通過抑制P-糖蛋白有助于吉非替尼透過體外血腦屏障模型。
[Abstract]:Aim: to establish a simple blood-brain barrier permeation model in vitro to study whether 尾 -elemene affects the transmembrane transport of gefitinib by inhibiting P- glycoprotein. Methods: the primary cultured rat brain microvascular endothelial cells and astrocytes were co-cultured in transwell to simulate the blood-brain barrier. The integrity of the barrier model was monitored by cell resistor and sodium fluorescein. The changes of P-glycoprotein function were measured by the osmotic coefficient of rhodamine 123, and the transmembrane transport capacity of gifitinib was measured by liquid-mass spectrometry and the apparent permeability coefficient was calculated. Results: the measured sodium fluorescein Pe was 4.90 鹵1.31 脳 10-6 cms-1, and the transmembrane resistance was 317.56 鹵19.34 cm-2, which revealed that the barrier model was successfully established. Elemene inhibited the transport of P-glycoprotein and increased the amount of Rhodamine 123 through the blood-brain barrier model, which revealed that elemene and gefitinib mediated the interaction through P-glycoprotein. Conclusion: elemene can promote the passage of gefitinib through the blood-brain barrier in vitro by inhibiting P- glycoprotein.
【學(xué)位授予單位】:中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2014
【分類號】:R96

【參考文獻】

相關(guān)期刊論文 前2條

1 劉愷鳴;遲路湘;魯向輝;何國祥;;大鼠腦微血管內(nèi)皮細胞的原代培養(yǎng)[J];第三軍醫(yī)大學(xué)學(xué)報;2007年20期

2 李s

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