江文章郭明良臺灣大學：施純光Shih, Chun-KuangChun-KuangShih2007-11-272018-06-292007-11-272018-06-292004http://ntur.lib.ntu.edu.tw//handle/246246/56381本研究目的為探討薏仁對大腸癌之影響，由四部分實驗組成。實驗一探討糙薏仁對大腸癌前期病變Aberrant crypt foci（ACF）的影響，雄性F344鼠餵食含不同劑量糙薏仁之飼料，以腹腔注射方式給予大腸癌致癌物Azoxymethane（AOM），於5週實驗期滿後取出大腸並檢查ACF。實驗結果顯示：無論飼料中糙薏仁含量為10 %、20 %或40 %，均可顯著降低ACF數及Aberrant crypt總數。代表ACF生長特質之腺窩多發性雖未顯著降低，但糙薏仁使各種大小的ACF數均降低。ACF主要出現在中段及遠端結腸，糙薏仁對中段結腸ACF的抑制效果較顯著。實驗二探討糙薏仁對大腸腫瘤及Cyclooxygenase-2（COX-2）的影響，雄性F344鼠餵食含不同劑量糙薏仁之飼料並注射AOM，於52週實驗期滿後取出大腸，檢查腫瘤並分析COX-2表現。實驗結果顯示：腫瘤多發性及腫瘤體積在各組間無顯著差異，而餵食20 %糙薏仁使近端結腸腫瘤發生率有較低的趨勢。對腫瘤COX-2表現的抑制效果以20 %糙薏仁較佳。實驗三探討糙薏仁成分對ACF及COX-2的影響，實驗結果顯示1.6 %薏苡麩皮抑制ACF的效果最佳。ACF主要出現在中段及遠端結腸，薏苡麩皮及精白薏仁對近端及遠端結腸ACF的抑制效果較顯著。糙薏仁成分可抑制結腸黏膜COX-2表現，其中薏苡麩皮的抑制效果較佳。實驗四探討糙薏仁成分對大腸癌前期病變發展的影響，實驗結果顯示糙薏仁、薏苡麩皮、薏苡麩皮乙醇萃取物均可抑制分泌混合型黏液素的ACF（MIX-ACF）。由以上研究結果推測：糙薏仁主要藉由麩皮於大腸癌形成過程之早期發揮抑制作用，其作用機制與改變大腸黏液素組成及抑制COX-2表現有關。This study consisting of four experiments investigated the effect of adlay on colon cancer. The first experiment investigated the effect of dehulled adlay on preneoplastic lesions, aberrant crypt foci (ACF). Male F344 rats were fed diets containing different doses of dehulled adlay and received the colon-specific carcinogen, azoxymethane (AOM), by intraperitoneal injection. All rats were killed after 5 weeks of feeding, and the colons were examined for ACF. Dietary dehulled adlay at levels of 10, 20, or 40% significantly reduced the numbers of ACF and aberrant crypts. Dehulled adlay reduced the number of ACF of different sizes but did not affect the crypt multiplicity. Most ACF were found in the middle and distal colons; dehulled adlay significantly suppressed the formation of ACF in the middle colon. The second experiment investigated the effect of dehulled adlay on colon tumors and cyclooxygenase (COX-2). Male F344 rats were fed diets containing different doses of dehulled adlay and injected with AOM. All rats were killed after 52 weeks of feeding, and colons were examined for tumors and COX-2 protein expression. The results indicated that dehulled adlay did not inhibit colon tumors in spite of a slight suppressing effect in the proximal colon by 20% dehulled adlay. Rats fed diets containing 20% dehulled adlay had less COX-2 protein expression in both proximal and distal colon tumors. The third experiment investigated the effect of dehulled adlay and its fractions on ACF and COX-2. Adlay bran at 1.6% level showed the best effect of ACF inhibition. Most ACF were found in the middle and distal colons; dehulled adlay and its fractions significantly suppressed the formation of ACF in the proximal and distal colons. Rats fed diets containing dehulled adlay and its fractions, especially adlay bran, had less COX-2 protein expression in the colonic mucosa. The forth experiment investigated the effect of dehulled adlay and its fractions on preneoplastic lesions. The results indicated that dehulled adlay, adlay bran, and ethanol extract of adlay bran suppressed ACF producing mixed types of mucin. These findings suggest that dehulled adlay suppresses early events in colon carcinogenesis by its bran fraction and these effects are associated with mucin alteration and COX-2 suppression in the colon.目錄------------------------------------------------------------------------------------------ I 表目錄--------------------------------------------------------------------------------------- IV 圖目錄--------------------------------------------------------------------------------------- VI 中文摘要------------------------------------------------------------------------------------ VII 英文摘要------------------------------------------------------------------------------------ VIII 第一章、總論------------------------------------------------------------------------------ 1 壹、緒言--------------------------------------------------------------------------------- 1 貳、文獻整理--------------------------------------------------------------------------- 3 一、薏苡------------------------------------------------------------------------------ 3 （一）薏苡簡介------------------------------------------------------------------- 3 （二）薏苡之成分---------------------------------------------------------------- 3 （三）薏苡之抗腫瘤作用------------------------------------------------------- 7 二、大腸癌--------------------------------------------------------------------------- 11 （一）大腸癌之威脅------------------------------------------------------------- 11 （二）大腸癌之形成------------------------------------------------------------- 11 （三）影響大腸癌之膳食因子------------------------------------------------- 12 （四）大腸癌之化學預防------------------------------------------------------- 13 （五）ACF與大腸癌------------------------------------------------------------- 14 （六）COX-2與大腸癌---------------------------------------------------------- 16 （七）黏液素與大腸癌---------------------------------------------------------- 17 三、大腸癌之動物模式------------------------------------------------------------ 18 （一）大腸癌動物模式簡介---------------------------------------------------- 18 （二）異種移殖模式------------------------------------------------------------- 18 （三）基因改造模式------------------------------------------------------------ 18 （四）化學誘發模式------------------------------------------------------------ 19 參、研究動機與目的------------------------------------------------------------------ 22 肆、實驗設計與架構------------------------------------------------------------------ 22 第二章、糙薏仁對鼠大腸癌前期病變ACF之影響------------------------------- 24 壹、前言--------------------------------------------------------------------------------- 24 貳、材料與方法------------------------------------------------------------------------ 26 一、實驗材料------------------------------------------------------------------------ 26 二、實驗方法------------------------------------------------------------------------ 27 參、結果與討論------------------------------------------------------------------------ 32 一、F344鼠攝食及生長狀況----------------------------------------------------- 32 二、糙薏仁對F344鼠大腸ACF數目及生長特質之影響------------------ 33 三、糙薏仁對F344鼠大腸ACF分布之影響--------------------------------- 38 肆、結論--------------------------------------------------------------------------------- 41 第三章、糙薏仁對鼠大腸腫瘤及COX-2之影響----------------------------------- 42 壹、前言--------------------------------------------------------------------------------- 42 貳、材料與方法------------------------------------------------------------------------ 44 一、實驗材料------------------------------------------------------------------------ 44 二、實驗方法------------------------------------------------------------------------ 47 參、結果與討論------------------------------------------------------------------------ 53 一、F344鼠攝食及生長狀況---------------------------------------------------- 53 二、糙薏仁對F344鼠大腸腫瘤之影響----------------------------------------- 55 三、糙薏仁對F344鼠大腸COX-2表現之影響------------------------------ 61 肆、結論--------------------------------------------------------------------------------- 65 第四章、薏仁成分對鼠大腸ACF及COX-2之影響--------------------------------- 66 壹、前言--------------------------------------------------------------------------------- 66 貳、材料與方法------------------------------------------------------------------------ 68 一、實驗材料------------------------------------------------------------------------ 68 二、實驗方法------------------------------------------------------------------------ 70 參、結果與討論------------------------------------------------------------------------ 75 一、F344鼠攝食及生長狀況----------------------------------------------------- 75 二、薏仁成分對F344鼠大腸ACF數目及生長特質之影響--------------- 76 三、薏仁成分對F344鼠大腸ACF分布之影響------------------------------ 79 四、薏仁成分對F344鼠大腸COX-2表現之影響--------------------------- 81 五、薏仁成分與作用之相關性分析--------------------------------------------- 82 肆、結論--------------------------------------------------------------------------------- 87 第五章、薏仁成分對鼠大腸癌前期病變發展之影響------------------------------- 88 壹、前言--------------------------------------------------------------------------------- 88 貳、材料與方法------------------------------------------------------------------------ 90 一、實驗材料------------------------------------------------------------------------ 90 二、實驗方法------------------------------------------------------------------------ 92 參、結果與討論------------------------------------------------------------------------ 97 一、F344鼠攝食及生長狀況----------------------------------------------------- 97 二、薏仁成分對F344鼠大腸ACF數目及生長特質之影響--------------- 98 三、薏仁成分對F344鼠大腸ACF分布之影響------------------------------ 102 四、薏仁成分對F344鼠大腸癌前期病變黏液素之影響------------------- 104 肆、結論--------------------------------------------------------------------------------- 109 第六章、綜合討論------------------------------------------------------------------------ 110 壹、化學誘發模式中大腸癌之形成過程------------------------------------------ 110 貳、糙薏仁之化學預防作用--------------------------------------------------------- 113 參、總結---------------------------------------------------------------------------------- 123 參考文獻------------------------------------------------------------------------------------ 1241016992 bytesapplication/pdfen-US薏仁Cyclooxygenase-2 (COX-2)大腸癌黏液素Aberrant crypt foci (ACF)Colon cancerMucinAdlay[SDGs]SDG3thesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/56381/1/ntu-93-D88641001-1.pdf