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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50559
完整後設資料紀錄
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dc.contributor.advisor潘敏雄
dc.contributor.authorYa-Chun Chouen
dc.contributor.author周雅淳zh_TW
dc.date.accessioned2021-06-15T12:46:09Z-
dc.date.available2021-09-22
dc.date.copyright2016-09-22
dc.date.issued2016
dc.date.submitted2016-07-25
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50559-
dc.description.abstract大腸直腸癌(colorectal cancer)逐漸成為全世界普遍盛行的癌症之一,流行病學研究指出發炎反應會加劇腫瘤的形成(tumorigenesis),其中乳香樹脂在印度傳統醫學中常用於治療多種發炎相關的疾病,本實驗所使用的天然物是乳香超臨界二氧化碳(CO2)萃取物,乳香樹脂中的主要成分為boswellic acids,利用LC-MS/MS分析萃取物中含有四種boswellic acids,包括β-boswellic acid、acetyl-β-boswellic acid、11-keto-β-boswellic acid和acetyl-11-keto-β-boswellic acid,雖然boswellic acids已被認為具有抗腫瘤生成的潛力,然而其機制尚不明確。故本實驗將更進一步以AOM/DSS致癌模式評估乳香萃取物抑制小鼠腸道腫瘤形成之功效,結果顯示在給予乳香萃取物之後可顯著提升小鼠存活率以及減少腸道腫瘤的形成,且從腸道組織分析的結果可以看出攝食乳香萃取物能藉由抑制NF-κB及調節MAPKs進而降低發炎酵素inducible nitric oxide synthase (iNOS)和cyclooxygenase-2 (COX-2)等之蛋白質表現量,此外乳香萃取物也能藉由減少磷酸化之Akt和GSK3β及其下游的cyclin D1來抑制細胞之增生。另外,我們也觀察到AOM/DSS誘導之小鼠在給予乳香萃取物後,能增加腸道中梭菌目(Clostridiales)的含量以及減少擬桿菌目(Bacteroidales)之比例。綜合以上結果我們認為乳香萃取物具有可發展為預防結腸直腸癌膳食補充劑之潛力。zh_TW
dc.description.abstractColorectal cancer (CRC) become a worldwide public health problem. In the previous studies, inflammation-linked carcinogenesis is well accepted concept and is often observed. Boswellia serrata resin has been used in India traditional medicine to treat a variety of inflammatory-related diseases. The most significant components of its supercritical CO2 extraction analysis by LC-MS/MS are boswellic acids including β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid. Although boswellic acids have been shown to be potential anti-tumorigenesis phytochemicals, but their mechanisms involved are not clear. In the present study, we investigated the chemopreventive effects of a Boswellia serrata (BS) extract on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon tumorigenesis in ICR mice. We found that the treatment with BS extract can restore the shortening of the colon length, enhance the survival rate and reduce the colonic tumor growth. Western blot and histological analysis revealed that dietary BS extract could markedly reduce the protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs) and nuclear expression of NF-κB. Furthermore, BS extract reduced cell proliferation via inhibiting phosphorylation level of Akt, GSK3β and downregulation of cyclin D1. In addition, we also observed the changes on colonic microbiota after fed with BS extract that enhanced the ratio of Clostridiales and decreased abundance of Bacteroidales in AOM/DSS-treated mice. These results suggest that dietary administration of BS extract may alleviate colonic tumorigenesis.en
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dc.description.tableofcontents謝誌 I
中文摘要 II
Abstract III
目錄 IV
附圖索引 VII
圖目錄 X
表目錄 XI
縮寫表 XII
第壹章、文獻回顧 1
第一節 大腸直腸癌(Colorectal cancer; CRC)之簡介 1
(一)大腸癌之流行病學概況 1
(二)大腸的構造及生理功能 3
(三)大腸直腸癌的分類 5
(四)大腸直腸癌的分期 6
(五)大腸直腸癌的形成過程 7
(六)人類基因表現與大腸癌的關係 8
(七)形成大腸癌之危險因子 10
第二節 發炎與腸癌的形成過程 14
(一)類二十碳酸(Eicosanoids)與癌症 14
(二) COX-2與細胞凋亡的關係 15
(三) COX-2促進腸癌的進展 16
(四) NF-κB的促發炎(pro-inflammation)機制與癌症形成之關係 16
(五) Nrf2的功能與細胞增生 19
(六) Nrf2的調控 20
第三節 細胞週期(Cell cycle) 22
(一)細胞週期的分期 22
(二)細胞週期的調控 22
(三)PI3K/Akt/GSK3β路徑在細胞週期中扮演的角色 25
第四節 腸道菌相(gut microbiota) 27
(一)腸道菌的分門 27
(二)正常腸道菌相與腸道障壁之維持 27
(三)腸道菌之代謝物(metabolites)與大腸癌 28
第五節 乳香(Boswellia serrata resin)之簡介 30
(一)乳香的來源及功效 30
(二)超臨界流體萃取乳香 30
(三) Boswellic acid analogs 32
第六節 誘導發炎之細胞模式 33
(一)巨噬細胞 33
(二)脂多醣(LPS)誘導發炎反應之機制 33
(三)一氧化氮(NO)與誘發型一氧化氮合成酶(iNOS) 34
第七節 誘發大腸癌之動物模式 35
(一)AOM/DSS二階段致癌模式 35
第貳章、實驗目的與架構 40
第一節 實驗目的 40
第二節 實驗架構 40
第參章、材料與方法 43
第一節 實驗材料 43
(一)儀器設備與耗材 43
(二)試劑與藥品 44
第二節 細胞試驗 45
(一)細胞培養 45
(二)細胞存活率測試 45
(三) Nitrie之測定 46
第三節 動物實驗 48
(一)動物來源及飼養方式 48
(二)AOM/DSS致癌模式 48
(三)蛋白質膠體電泳(SDS-PAGE)與西方墨點法 50
(四)組織的脫水、包埋與切片 54
(五)Hematoxylin & eosin stain 56
(六) Immunohistochemistry (IHC) stain 57
(七)腸道菌相分析 60
第四節 統計分析 63
第肆章、結果 64
第一節、乳香(BS)萃取物能減少LPS所誘導之小鼠巨噬細胞RAW264.7的一氧化氮(NO)生成 64
第二節、乳香(BS)萃取物對AOM誘導之小鼠所產生的生理變化及腸道組織型態的影響 64
第三節、乳香(BS)萃取物改善AOM/DSS誘導之小鼠腫瘤的形成 65
第四節、乳香(BS)萃取物藉由降低發炎反應及MAPKs的活性抑制AOM/DSS所誘導的腸道腫瘤生成 66
第五節、乳香(BS)萃取物透過調節PI3K/Akt路徑抑制腫瘤細胞的增生 67
第六節、乳香(BS)萃取物對AOM/DSS誘導之小鼠糞便中菌相的影響 68
第伍章、討論 69
第陸章、結論 72
第柒章、圖表 73
第捌章、參考文獻 86
第玖章、附錄 92
dc.language.isozh-TW
dc.subject乳香zh_TW
dc.subject腸道菌zh_TW
dc.subjectAzoxymethane/Dextran sulfate sodium (AOM/DSS)zh_TW
dc.subject發炎zh_TW
dc.subject大腸癌zh_TW
dc.subject乳香zh_TW
dc.subject腸道菌zh_TW
dc.subjectAzoxymethane/Dextran sulfate sodium (AOM/DSS)zh_TW
dc.subject發炎zh_TW
dc.subject大腸癌zh_TW
dc.subjectBoswellia serrata (BS)en
dc.subjectcolorectal cancer (CRC)en
dc.subjectinflammationen
dc.subjectAzoxymethane/Dextran sulfate sodium (AOM/DSS)en
dc.subjectgut microbiomeen
dc.subjectBoswellia serrata (BS)en
dc.subjectcolorectal cancer (CRC)en
dc.subjectinflammationen
dc.subjectAzoxymethane/Dextran sulfate sodium (AOM/DSS)en
dc.subjectgut microbiomeen
dc.title乳香萃取物透過抑制發炎相關路徑減緩AOM/DSS所誘發的大腸腫瘤生成zh_TW
dc.titleBoswellia Serrata resin extract alleviates azoxymethane/dextran sulfate sodium-induce colon tumorigenesis via inhibition of inflammation related signaling pathwaysen
dc.typeThesis
dc.date.schoolyear104-2
dc.description.degree碩士
dc.contributor.oralexamcommittee何元順,王朝鐘,郭靜娟,何其儻
dc.subject.keyword乳香,大腸癌,發炎,Azoxymethane/Dextran sulfate sodium (AOM/DSS),腸道菌,zh_TW
dc.subject.keywordBoswellia serrata (BS),colorectal cancer (CRC),inflammation,Azoxymethane/Dextran sulfate sodium (AOM/DSS),gut microbiome,en
dc.relation.page92
dc.identifier.doi10.6342/NTU201601221
dc.rights.note有償授權
dc.date.accepted2016-07-25
dc.contributor.author-college生物資源暨農學院zh_TW
dc.contributor.author-dept食品科技研究所zh_TW
顯示於系所單位:食品科技研究所

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