臺灣博碩士論文加值系統

近年來許多研究報告紛紛出爐，指出嚼食檳榔可能誘發其他多種系統疾病，包括氣喘(asthma) 、心律不整(cardiac arrhythmia) 、糖尿病(diabetes) 、免疫系統之影響、呼吸系統疾病、心血管系統、消化系統、神經系統功能、泌尿生殖系統之障礙等。嚼食檳榔對神經系統之影響已被確定，可在中樞神經系統與末梢神經系統而產生不同的影響，主要是因為檳榔子（Betel nut）中的檳榔素(Arecoline)與檳榔次鹼(Arecaidine)有關，這兩種檳榔生物鹼(alkaloids)可作用在毒蕈鹼受體(muscarinic receptor) 。 GABA為中樞神經系統中主要的抑制性神經傳導物質，目前已知有三種GABA 受體存在：GABAA、GABAB 與GABAC 受體，過去研究證實周邊神經與組織也有GABA與其受體的存在，GABA 是CNS 中最主要的抑制性神經傳導物質，參與約30% 的腦神經突觸的訊息傳遞，並且調節大部分神經的生理活動。本實驗目的以檳榔萃取液餵食實驗動物，藉由天數不同觀察雄鼠各個腦區其GABA Receptor的表現量，在實驗中我們使用（100 mg/kg/day）荖花檳榔劑量，以餵管方式分別餵食三組(15、30、45天)並犧牲取全腦，萃取mRNA並以RT-PCR方式反轉錄cDNA，再以Real – Time PCR分析其基因表現量。研究結果發現以檳榔萃取液餵食45天的雄鼠，其GABAA Receptor表現量明顯上升，顯示檳榔萃取液可促進老鼠腦部之GABAA Receptor表現量。另外，我們利用西方墨點法的技術來觀察是否GABAA Receptor的蛋白質表現量，經由ERK/MAPK pathway的調控，跟mRNA表現量一致。在未來我們將陸續進行一系列檳榔與神經系統的研究，獲得更多科學證據證明檳榔對於神經系統的傷害，並期盼未來研究能作為臨床醫學上之參考指標，藉此讓國人與衛生單位重視此現象，進而達到宣導與預防之目標。

ABSTRACT
It is estimated that 2 million person in Taiwan have the habit of chewing betel. Reports have shown that chronic betel quid (BQ) chewing is associated with diverse systemic effects, including , Diabetes Hypertension,Metabolic syndrome. There are four main arecal alkaloids, arecoline,arecaidine, guvacine and guvacoline. They also bind to GABA receptors in the brain, contributing to their psychoactive effects. Arecoline is not a simple activating ligand for the GABA receptor since it acts as a GABA receptor `blocker’, preventing normal GABA inhibition of neurotransmission. Previous studies show that chewing BQ may affect the nervous system.We investigated whether administration of Betel Quid Extraction (BQE) induces nervous transmission in the brain of SD rats. BQE (100mg/kg weight/day) was administered orally for 15, 30, 45 day.In addition, parameters studied inlucued the time course of mRNA expression of induced by BQE in SD rats.The results showed that GABRE gene mRNA expression to appear up-regulation. Mitogen - activated protein kinase superfamilies, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38, together with transcription factor GABRE, are important signaling elements. We examined the activation of these signaling pathways in SD Rat, treated with Betel Quid Extraction (BQE).In addition, recent reports have raised the potential links between BQ chewing and cancers of oropharynx, esophagus, stomach, urinary bladder and liver. Further in-depth studies are needed to highlight the association between BQ chewing and the body health.

目錄
中文摘要……………………………………………………………… ii
英文摘要…………………………………………………………… iv
致謝………………………………………………………………… v
目錄…………………………………………………………………… vi
縮寫表……………………………………………………………… vii
第一章 緒論………………………………………………… 1
第一節 前言……………………………………………………… 1
第二章 文獻探討
第一節 檳榔及其相關成分…………………………………………4
第二節 檳榔對神經系統的影響……………………………………6
第三節 GABA………………………………………………………8
(一) 中樞神經系統………………………………………… 9
(二) 周邊系統………………………………………………10
第四節 GABAA 受體…………………………………………… 11
第五節 Mitogen-activated protein kinase (MAPK) 訊息傳遞路徑
與細胞凋亡……………………………………………… 12
第六節 十個基因簡介…………………………………………… 15
第三章 目的………………………………………………… 19
第四章 材料與方法………………………………………… 20
第一節 實驗設計…………………………………………………20
第二節 實驗動物…………………………………………………20
第三節 實驗前處理與方法………………………………………21
第四節 組織Total RNA萃取…………………………………….25
第五節 反轉錄PCR分析……………………………………… 26
第六節 即時聚合酶鏈鎖反應……………………………………27
第七節 組織蛋白質萃取…………………………………………29
第八節 西方墨點法分析…………………………………………31
第五章 結果………………………………………………… 35
第六章 討論………………………………………………… 38
第七章 結論………………………………………………… 41
參考文獻…………………………………………………… 42
表與圖……………………………………………………… 48
附錄………………………………………………………… 61

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李啟賓:檳榔萃取液對雄鼠內生性抗氧化作用及生殖效應之研究，大
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鄭景暉. 嚼食檳榔的健康危害(不包括口腔癌與口腔癌前病變), 中華
民國92年.