棕櫚酸對星狀膠細胞之毒性與兒茶素之保護機制

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题名:	棕櫚酸對星狀膠細胞之毒性與兒茶素之保護機制 Palmitic Acid-Induced Lipotoxicity and Its Protection by (+)-Catechin in Rat Cortical Astrocytes
作者:	巫鈺茹;Yu-Ju Wu
贡献者:	神經科學與認知科學研究所碩士班
关键词:	棕櫚油;星狀細胞;兒茶素;脂質毒殺;氧化壓力;粒線體;Palmitic acid;astrocytes;(+)-catechin;lipotoxicity;reactive oxygen species;mitochondrial membrane potential
日期:	2013-06-24
上传时间:	2016-01-08 15:23:37 (UTC+8)
出版者:	中國醫藥大學
摘要:	星狀細胞除了調節大腦代謝平衡外，還主動調控神經所釋放的神經傳導物質，避免神經傳導物質過多而傷害到腦細胞。棕櫚油為一種飽和脂肪酸，當我們人體攝入過多此類油脂會造成脂肪囤積，這些脂質隨時間持續囤積會惡化為腦中風或糖尿病等代謝性疾病。過去研究已證實，棕櫚油囤積會造成神經退化及發炎反應。而棕櫚油對於星狀細胞的直接傷害仍未被廣泛研究，本研究目的為探討棕櫚油對星狀細胞傷害之機轉及綠茶中的兒茶素是否能保護棕櫚油所造成的細胞傷害。研究結果顯示棕櫚油(100 μM)會使星狀細胞產生凋亡現象，並促使粒線體膜電位改變而大量釋放自由基造成星狀細胞的傷害。此研究結果並未發現棕櫚油所造成的細胞凋亡與細胞內鈣離子濃度、內質網壓力之直接關係。研究結果亦顯示棕櫚油(100 μM)對星狀細胞產生的凋亡現象，可以被綠茶中的兒茶素(300 μM)保護。 Astrocytes do not only maintain extra-neuronal homeostasis, but also play an active role in modulating synaptic transmission by releasing gliotransmitters. Palmitic acid (PA) is a saturated fatty acid which, when being excessive, is a significant risk factor for development of metabolic syndromes or stroke. Activation of astrocytes by PA has been shown to cause neuronal inflammation and demyelination. However, direct damage by PA to astrocytes is relatively unexplored. The aim of this study was to identify the mechanism(s) of PA-induced cytotoxicity in rat cortical astrocytes. Exposure of astrocytes to PA (100 μM) for 24 h resulted in approximately 50 % cell death. Cell death was apoptotic (as revealed by TUNEL assay) and unrelated to endoplasmic reticulum (ER) stress and cytosolic Ca2+ elevation. Exposure of astrocytes to PA for 30 min to 5 h was associated with significant mitochondria membrane potential (MMP) collapse and reactive oxygen species (ROS) production. Co-treatment of astrocytes with (+)-catechin (300 μM), an anti-oxidant found abundantly in green tea, significantly prevented PA-induced MMP collapse, ROS production and cell death. Our results suggest that PA-induced cytotoxicity in astrocytes may involve MMP collapse and ROS production, which can be prevented by (+)-catechin.
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