槲皮素藉由增加粒線體生合成之作用降低氧化壓力對於人類神經纖維瘤母細胞株之傷害

Quercetin protects human neuronal SH-SY5Y cells against oxidative stress-induced damage by increasing mitochondrial biogenesis and reducing free radicals

何佳玲(Chia-Ling Ho)

指導教授 ： 林士祥

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/碩士(2014年)

摘要

神經細胞粒線體由細胞本體所生成，運輸至軸突及樹突供細胞所需，維持細胞功能，而氧化壓力為造成神經退化性疾病的危險因子之一，隨著年紀的老化，腦部粒線體生合成能力降低，且活性氧屬的產生及堆積，影響腦部正常功能。類澱粉樣蛋白質堆積為阿茲海默症的病理特徵之一，過去研究指出，阿茲海默症患者腦部粒線體生合成顯著降低。槲皮素為一黃酮類物質，廣泛存在於蔬菜及水果中，過去文獻指出，槲皮素在細胞實驗中發現其具有促進粒線體生合成之功用。研究目的：探討槲皮素是否會藉由提升粒線體生合成進而影響神經細胞內類澱粉樣蛋白堆積程度。材料方法：本試驗以人類纖維母細胞株SH-SY5Y為神經細胞模式，先給予槲皮素再給予過氧化氫處理，觀察細胞內粒線體生合成及功能變化，並且檢測類澱粉樣裂解路徑相關酵素蛋白表現量及細胞凋亡程度。結果：過氧化氫會促使細胞內活性氧屬堆積及降低粒線體生合成及細胞內ATP產生量，造成類澱粉樣蛋白質堆積及細胞凋亡現象，然而，事先給予槲皮素則可提高粒線體的生合成，增加細胞內ATP產生量，進而減緩細胞受到氧化壓力造成的傷害，降低類澱粉樣蛋白質堆積及細胞凋亡現象，對於細胞產生保護作用。

關鍵字

類澱粉樣蛋白質 ； 氧化壓力 ； 槲皮素 ； 粒線體生合成 ； 細胞內ATP產生量 ； 神經退化性疾病

並列摘要

Background： Present studies suggested that lack of mitochondrial biogenesis in Alzheimer’s disease patient’s brain. Quercetin, has been shown to increase mitochondrial biogenesis. Purpose：Our purpose was to exam whether quercetin can increase mitochondrial biogenesis to ameliorate beta amyloid accumulation in H2O2-induced SH-SY5Y neuron cell. Methods: SH-SY5Y cell were treated H2O2 to induce oxidative stress. We pretreated 0, 2.5, 5, 7.5, 10 μM quercetin then to analyze the cellular mitochondrial biogenesis, ATP production and cell apoptosis in H2O2 induced cell. We measured SIRT1, PGC-1α, TFAM, ADAM10, BACE and Aβ levels in SH-SY5Y after quercetin and H2O2 were treated. Results：We found quercetin increased SIRT1, PGC-1α and TFAM level to increase mitochondrial biogenesis. Quercetin treatments also increased ADAM10 level and decrease BACE level to inhibit beta amyloid accumulation in H2O2-induced SH-SY5Y neuron cell. Moreover, decreasing in cell apoptosis was observed in quercetin pretreated SH-SY5Y neuron cell. Conclusion：Querctin can protect cell from H2O2 induced oxidative stress by elevating mitochondrial biogenesis and decreasing beta amyloid accumulation.

並列關鍵字

beta amyloid ； oxidative stress ； quercetin ； mitochondrial biogenesis ； ATP production ； neurodegenerative disease

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