建立體外血腦屏障細胞模型以測試藥物之通透性

Establishment of an in vitro Model of Blood-brain Barrier for Permeability Test of Potential Drugs

陳泰元(Tai-Yuan Chen) ； 蘇伯憲(Po-Hsien Su) ； 李政怡(Cheng-I Lee)

《化學》 73卷3期 (2015/09) Pp. 181-185

https://doi.org/10.6623/chem.2015018

摘要

現今在治療腦部疾病上，主要以藥物治療的為主，而藥物開發上存有治療藥物是否能通過血腦屏障的疑慮。故目前必須解決的問題之一，就是建立體外之血腦屏障細胞模型，用以測試藥物是否能有效的通過血腦屏障，以期提升治療成效。因此，我們利用老鼠細胞建立一個體外的血腦屏障細胞模型，並以該模型進行細胞通透性測試。在我們的實驗中，利用插入式細胞培養皿(transwell)建立體外血腦屏障細胞模型。首先在插入式細胞培養皿的插入層(insert)中，將老鼠內皮細胞(b.End 3)與星狀細胞(ALT)進行接觸式培養，以建立實驗的體外細胞模型，並以緊密連接(tight junction)蛋白(occludin)的表達量、跨上皮電阻值，確認此模型可代表血腦屏障。透過這樣的實驗，我們期望能利用這個模型，尋找出具有良好通透性的藥物，以利往後腦部相關研究、治療腦部疾病的方法。

關鍵字

腦 ； 血腦屏障 ； 通透性 ； 插入式細胞培養皿 ； 緊密連接 ； 跨上皮電阻

並列摘要

The most common therapy of brain diseases is chemotherapeutic treatment. However, most of chemotherapeutic drugs cannot pass through the blood-brain barrier (BBB). This BBB decreases the efficiency of chemical combination therapy. For efficient development of drugs for brain diseases, a cell model for blood-brain barrier is highly required. Therefore, we built an in vitro blood-brain barrier model based on mouse cells to test the permeability of compounds. We used transwells to build BBB cell model starting from the co-culture of endothelial (b.End 3) and astrocyte (ALT) cells with cell-cell contact in the insert of transwells. To test the representative of this model, we monitored the formation of the tight junction by the expression level of occludin, a tight-junction protein, and trans-epithelial electrical resistance. Based on this model, we expect to find potential drugs with good permeability to BBB for further brain research and drug development for brain diseases.

並列關鍵字

Brain ； Blood-brain barrier ； Permeability ； Transwell ； Tight-junction ； Trans-epithelial electrical resistance