以高脂低纖維合併化學致癌之大腸癌模式探討膳食纖維之預防作用

To Investigate effects of Dietary Fiber on High-fat Low-fiber Diet with AOM-induced Colon Carcinogenesis in C57BL/6J Mice

蕭秀娟(Hsiu-Chuan Hsiao)

指導教授 ： 陳曉鈴

中山醫學大學/健康管理學院/營養學系碩士班/碩士(2012年)

摘要

本實驗室先前研究發現蒟蒻纖維(KGM)及菊糖(Inulin)具有增加糞便實體、助於腸道蠕動利於排出有害物質、促進腸道益生菌生長、增加短鏈脂肪酸產生、降低糞便水基因毒性及DNA傷害等良好功效，因此推測蒟蒻纖維及菊糖具有保護大腸表皮細胞潛力，達到抑制大腸癌發生的作用。根據國民營養調查結果得知國人飲食習慣偏向高油脂低纖維飲食，這種飲食型態可能增加結腸癌的危險性。因此，為了證實在高油脂低纖維的飲食情況下額外添加膳食纖維具有預防大腸癌危險因子的作用，本研究初步建立高脂低纖維合併azoxymethane (AOM)化學致癌的大腸癌前期病變模式，並探討不同劑量之蒟蒻纖維及菊糖降低結腸異常腺窩病灶(aberrant crypt foci, ACF)發生的可能機制。
將六週齡之C57B/6J雄性小鼠隨機分為下列幾組：vehicle控制組(腹腔注射生理食鹽水，1次/週×7，20%玉米油及1%纖維素飲食)及AOM控制組(10 mg/kg BW)，以及AOM注射並於控制飼料中添加不同程度纖維之L-KGM組(2.5% w/w)、H-KGM組(5% w/w)、L-Inulin組及H-Inulin組。實驗分別於30週及45週後進行犧牲，分析大腸癌前指標—結腸異常腺窩病灶(ACF)、體內抗氧化指標(血液單核球細胞DNA損傷與血液脂質過氧化物濃度)、發炎相關指標(血液細胞激素濃度)及腸道環境因子(糞便短鏈脂肪酸濃度與糞便菌相)。
結果顯示AOM組之後端結腸病灶數目以及每個病灶所含異常腺窩數目顯著高於補充膳食纖維的組別。AOM具有增加血液過氧化壓力的作用，補充蒟蒻或菊糖後皆可有效改善血液單核球之DNA損傷情形以及脂質過氧化物濃度。AOM同時提高趨發炎反應，補充蒟蒻或菊糖後均可抑制促發炎激素Tumor Necrosis Factor-α (TNF-α)、Interleukin-1β (IL-1β)及Interleukin-6 (IL-6)分泌並提高抑發炎激素Interleukin-10 (IL-10)分泌。在腸道環境因子方面，補充蒟蒻或菊糖後均可促進Bifidobacterium spp.及Lactobacillus spp.生長並抑制Clostridium spp.孳生。
本研究建議蒟蒻纖維及菊糖可能藉由調控腸道微生物代謝及體內發炎反應來減少大腸癌病變的發生

關鍵字

大腸癌 ； azoxymethane (AOM) ； 膳食纖維 ； 異常腺窩病灶 ； aberrant crypt foci (ACF)

並列摘要

Previous studies have shown that konjac glucomannan (KGM) and inulin beneficially modulated bowel movement, microflora, short chain fatty acid production, and reduce toxin formation and fecal water toxicity. Therefore, we hypothesized that konjac glucomannan and inulin could protect the large intestine from colorectal carcinogenesis. The Nutrition and Health Survey in Taiwan indicates a trend of high-fat low-fiber dietary habit, which could lead to greater risk for colon cancer. In order to determine the role of dietary fibers on prevention of colorectal cancer occurrence and progression, we investigated effects of konjac glucomannan and inulin supplementation into a high-fat low-fiber diet on an azoxymethane (AOM)-induced colon cancer rodent model.
C57B/6J male mice (6 weeks of age) were randomly divided into the following groups: vehicle (saline i.p., once per week for 7 weeks) control (high-fat 20% corn oil, low-fiber 1% cellulose diet), and AOM (10 mg/kg BW) groups that were fed control, L-KGM (2.5% w/w), H-KGM, L-Inulin group or H-Inulin diet. Mice were sacrificed after 30 and 45 weeks, respectively. The precancerous indicators—aberrant crypt foci (ACF), antioxidant indicators (DNA damage of peripheral blood mononuclear cell, blood lipid peroxide concentration), blood cytokine concentration (TNF-α, IL-1, IL-6, IL-10) and the intestinal factors (fecal short-chain fatty acid concentrations, fecal bacteria) were determined.
Results indicated that the number and multiplicity of ACF in the distal colon were enhanced with AOM injection, which was significantly lowered in fiber-supplemented groups. Low and high levels of KGM or inulin supplement significantly reduced the DNA damage of peripheral blood mononuclear cells and plasma pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) levels and promoted the plasma anti-inflammatory cytokine IL-10 levels. Either level of KGM or inulin supplement increased the fecal Bifidobacterium spp. and Lactobacillus spp. concentrations, and inhibited the Clostridium spp. concentration.
Therefore, these results suggest that KGM and inulin may reduce the occurrence and progression of colon carcinogenesis since the initiation stage through the regulation of intestinal microflora metabolism and inflammatory responses.

並列關鍵字

colon cancer ； azoxymethane (AOM) ； konjac glucomannan (KGM) ； inulin ； dietary fiber ； aberrant crypt foci (ACF)

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