Nicardipine在微膠細胞抑制神經性發炎反應的作用

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Title:	Nicardipine在微膠細胞抑制神經性發炎反應的作用 Nicardipine suppresses neuroinflammatory responses in microglial cells
Authors:	黃伯仁;Bor-Ren Huang
Contributors:	臨床醫學研究所碩士班
Keywords:	神經性發炎反應;微膠細胞;nicardipine;microglia;anti-inflammation
Date:	2013-07-29
Issue Date:	2013-10-02 11:22:24 (UTC+8)
Publisher:	中國醫藥大學
Abstract:	Nicardipine 是一種鈣離子阻斷劑，有很好的降血壓的效果。它常被用來治療因為缺血性中風、外傷性腦損傷及出血性腦中風後引起的危害性高血壓。而且因為降血壓效果穩定且快速，又沒有其他心肺方面的抑制效果，所以逐漸被廣泛且常規的使用在神經加護照顧。但是這個藥物在神經細胞的作用機制目前仍不清楚。我們利用老鼠的微膠細胞 (microglia) 培養實驗，發現nicardipine 有明顯的抑制神經細胞發炎反應的效果。而且在動物實驗上也發現nicardipine能抑制微膠細胞 (microglia) 的活化達到神經保護的效果，我們同時也發現nicardipine會抑制微膠細胞因ATP所活化的移行反應。Nicardipine 會減少經由LPS/IFN-γ所刺激的微膠細胞 (microglia) 之NO生成量，同時也會抑制 iNOS 和 COX-2 的表現，對於前驅發炎細胞因子 IL-6 及IL-1β也有抑制的效果。由進一步的實驗顯示，nicardipine 有可能是藉由抑制MAPK/Akt pathway 中的Akt, p38、p65 及 cJun之磷酸化作用，進一步抑制 NF-κB pathway之活化來達到抗神經性發炎的效果。 Nicardipine hydrochloride, a calcium channel blocker (CCB), has strong anti-hypertensive activity. It has been used to control blood pressure in severe hypertension after ischemic stroke, traumatic brain injury, and intracerebral hemorrhage (ICH) and increasingly widely applied in neurointensive care. But the definite response of nicardipine on neuron cells is unclear. Using the murine BV-2 microglia in culture, we demonstrated the nicardipine significantly inhibited LPS/IFN-γ-induced neuroinflammatory response. The neuroprotective effect of nicardipine was attributed to the inhibition of microglial activation in animal model, and significantly inhibited the production of nitric oxide (NO). We also found that nicardipine inhibited the migration of microglia cells which were activated by ATP. Nicardipine down-regulates LPS/IFN-γ induced nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) expression in BV-2 microglia, too. Hereafter nicardipine effectively suppressed pro-inflammtory cytokines expression such as IL-6 and IL-1β. Furthermore, nicardipine inhibited the phosphorylated of p38 and Akt in BV-2 microglia and suppressed the phosphorylated of p65 and cJun. Our data showed that nicardipine hydrochloride significantly suppress MAPK/Akt signaling pathway activation, which is involved in anti-neuroinflammation.
Appears in Collections:	[Graduate Institute of Clinical Medical Science] Theses & dissertations

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