臺灣博碩士論文加值系統

芝麻素Sesamin已知具有很好的抗氧化與清除自由基之能力，所以可以使用於神經保護之功能。我們是以卡英酸引發神經興奮毒性之癲癇模式，並且利用芝麻素神經保護之特性，探討卡英酸引發神經細胞株PC12與神經微膠細胞株BV-2的神經興奮毒性的芝麻素神經保護之能力與機轉。
本研究證實，芝麻素可以有效降低PC12與BV-2細胞的神經興奮傷害(MTT, LDH)，與降低因細胞傷害之鈣離子釋放量；芝麻素可以清除活性氧自由基、降低脂質過氧化物含量、與降低神經發炎因子-前列腺素 E2 之釋放量；由細胞傳遞路徑實驗結果顯示，芝麻素明顯降低 JNK、ERK、p38 MAPKs、caspase-3 、Rho A、與COX-2 等蛋白質表現量，在離體實驗證實，芝麻素可以有效的降低卡英酸所造成之神經興奮傷害，是藉由降低神經細胞凋亡作用 (p38 MAPKs、caspase-3)，與降低神經發炎反應 (COX-2)。
本研究印證芝麻素可以有效的減緩卡英酸誘導所產生的神經興奮之傷害，是綜合性地藉由清除活性氧自由基、降低神經細胞凋亡作用、與降低神經發炎反應，來達成神經保護之功能。

Sesamin, a lignan from sesame oil, has been shown to have antioxidative properties. Kainic acid (KA)-induced status Epilepsy was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. Sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA), neurodegeneration (Caspase-3), and inflammation (COX-2) in PC12 cells.Sesamin was effective to protect PC12 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 MAPKs mitogen-activated protein kinases and COX-2 expression in both cells and RhoA expression in PC12 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation. Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory, anti-apoptosis and partially antioxidative mechanisms.

封面 I
致謝 II
縮寫對照表 III
中文摘要 IV
英文摘要 V
目錄 VI
圖目錄 VIII
第一章 緒論 1
1.1 癲癇 1
1.2 卡英酸 (Kainic acid, KA) 3
1.3 神經系統內的細胞 11
1.3.1 嗜鉻性神經細胞瘤細胞 PC12 cells 12
1.3.2 神經微膠細胞 BV-2 cells 14
1.4 芝麻素Sesamin 16
1.5 研究目的 19
第二章 材料與方法 20
2.1 藥品 20
2.2 儀器 20
2.3 試劑Reagents 20
2.4 細胞培養 23
2.5 細胞存活率試驗 24
2.6 細胞傷害試驗 25
2.7 鈣離子含量試驗 26
2.8 清除活性氧化物能力試驗 27
2.9 一氧化氮自由基含量測試 28
2.10 細胞內蛋白質萃取 29
2.11 細胞內特異性蛋白質含量試驗 29
2.12 脂質過氧化物含量試驗 31
2.13 凋亡蛋白Caspase-3 表現 33
2.14 前列腺素E2 含量試驗 34
2.15 統計分析 (Statistical analysis) 35
2.16 實驗流程 36
第三章 結果 37
3.1 KA誘導產生癲癇模式下SA保護PC12細胞存活率與細胞傷害之影響 37
3. 2 KA誘導產生癲癇模式下SA保護PC12細胞鈣離子含量之影響 39
3.3 KA誘導產生癲癇模式下SA保護PC12細胞清除活性氧化物能力 41
3.4 KA誘導產生癲癇模式下SA保護PC12細胞脂質過氧化物含量 43
3.7 KA誘導產生癲癇模式下SA保護PC12細胞前列腺素 E2含量測定 45
3.5 KA誘導產生癲癇模式下SA保護PC12細胞之分子機制路徑 47
3.6 KA誘導產生癲癇模式下SA保護PC12細胞凋亡蛋白Caspase-3含量 50
3.8 KA誘導產生癲癇模式下SA保護BV-2細胞存活率與細胞毒性之影響 52
3.9 KA誘導產生癲癇模式下SA保護BV-2細胞鈣離子含量之影響 54
3.10 KA誘導產生癲癇模式下SA在BV-2細胞中一氧化氮含量 56
3.11 KA誘導產生癲癇模式下SA保護BV-2細胞清除活性氧化物能力 58
3.13 KA誘導產生癲癇模式下SA保護BV-2細胞前列腺素 E2含量測定 60
3.12 KA癲癇模式下SA保護BV-2細胞之分子機制路徑 62
第四章 討論 65
第五章 結論 69
參考文獻 70
附件 80

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