檳榔鹼對於分化後的神經原母細胞SH-SY5Y及小神經膠細胞BV-2的作用

Effect of arecoline on differentiated neuroblastoma SH-SY5Y cells and microglia BV-2 cells

吳季翰(Chi-Han Wu)

指導教授 ： 羅怡卿

高雄醫學大學/醫學院/藥理學科研究所/碩士(2009年)

摘要

檳榔主要成分中的檳榔鹼(arecoline)經研究證實會引起口腔癌及食道癌。近來臨床上因arecoline具有擬膽鹼作用，已經將低劑量arecoline應用於阿茲海默症(Alzheimer's disease)的治療中。然而，arecoline對神經及小神經膠細胞的作用尚有不清楚。本研究的目的是探討arecoline對於分化之神經細胞(SH-SY5Y)及小神經膠細胞(BV-2)的之作用。實驗結果顯示高濃度arecoline (100-400 uM)會降低神經細胞的存活現象。arecoline會增加SH-SY5Y細胞的Bax蛋白質表現以及降低Bcl-2的蛋白質表現，進而降低Bcl-2/Bax ratio。Arecoline亦會減少pro-caspase 3的表現。此外，arecoline會誘發SH-SY5Y之COX-2及nNOS蛋白質的表現。至於BV-2 細胞實驗結果則顯示arecoline會增加細胞COX-2蛋白質的表現及PGE2的釋放量。Arecoline 會增加BV-2細胞之IkB-a及IkB-b的降解及增加NF-kB蛋白質的表現。Arecoline亦會誘發HO-1的蛋白質表現。總結，高濃度之arecoline可能經由Bcl-2/Bax以及capase 3相關路徑引起神經細胞的死亡，並且可能會增加小神經膠細胞之發炎反應。

關鍵字

檳榔鹼 ； 神經毒性 ； 發炎

並列摘要

Arecoline, a major alkaloid of betal nut, has been confirmed its relationship with oral and pharyngeal cancers. Recently, low dose of arecoline has been applied in the remedy of Alzheimer’s disease with its cholinergic agonist character. However, the effects of arecoline on the neuron and microglia remain unclear. The aim of this study was to investigate the effect of arecoline on differentiated neuronal SH-SY5Y cells and microglia BV-2 cells. In SH-SY5Y cells, arecoline (100-400 uM) decreased cell viability. Arecoline attenuated Bcl-2 expression and enhanced Bax expression, and therefore decreased Bcl-2/Bax ratio. Arecoline also decreased pro-caspase 3 expression and increased expression of COX-2 and nNOS. In BV-2 cells, arecoline increased COX-2 expression and PGE2 level. Arecoline decreased the expression of IkB-a?nand IkB-b?z which was accompanied by increase of NF-kB expression. Arecoline also enhanced HO-1 expression. In conclusion, high concentration of arecoline might induce neuronal cell death by activating Bcl-2/Bax- and caspase-associated pathways, and it might increase inflammatory responses in microglia cells.

並列關鍵字

arecoline ； neurotoxicity ； inflammation

參考文獻

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