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β-榄香烯对吉非替尼在体外血脑屏障模型中转运的影响

发布时间:2018-02-26 07:36

  本文关键词: β-榄香烯 吉非替尼 血脑屏障 P-糖蛋白 非小细胞肺癌 出处:《中国人民解放军医学院》2014年硕士论文 论文类型:学位论文


【摘要】:目的:建立简单的体外血脑屏障渗透模型研究β-榄香烯是否通过抑制P-糖蛋白影响吉非替尼的跨膜转运。 方法:在transwell装置中原代培养的大鼠脑微血管内皮细胞和星型胶质细胞建立共培养去模拟体内血脑屏障。用细胞电阻仪和荧光素钠来监测屏障模型的完整性。运用罗丹明-123渗透系数大小来衡量P-糖蛋白功能变化。液质联用方法测量吉非替尼的跨膜转运量并计算表观渗透系数. 结果:测得的荧光素钠Pe为4.90±1.31×10-6cms-1,跨膜电阻值为317.56±19.34cm2,,揭示成功建立屏障模型。在和榄香烯合用时,吉非替尼透过模型增加2.3倍。机制上,榄香烯抑制P-糖蛋白的转运增加了罗丹明123的透过血脑屏障模型量,揭示了榄香烯和吉非替尼通过P-糖蛋白介导产生了相互作用。 结论:榄香烯通过抑制P-糖蛋白有助于吉非替尼透过体外血脑屏障模型。
[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 卤1.31 脳 10-6 cms-1, and the transmembrane resistance was 317.56 卤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.
【学位授予单位】:中国人民解放军医学院
【学位级别】:硕士
【学位授予年份】:2014
【分类号】:R96

【参考文献】

相关期刊论文 前2条

1 刘恺鸣;迟路湘;鲁向辉;何国祥;;大鼠脑微血管内皮细胞的原代培养[J];第三军医大学学报;2007年20期

2 李s

本文编号:1537112


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