- 學位論文
優酪乳對DMH誘發F344鼠大腸癌前期病變之預防效果
Preventive effects of yogurt on DMH-induced preneoplastic lesions of colon in F344 rats
摘要
惡性腫瘤位居台灣十大死因之首，其中結腸直腸癌(大腸癌)在癌症死因中排名第三位，飲食與大腸癌發生最具關聯性。優酪乳是以牛奶為基礎，用益生菌作為發酵菌而製成的產品，先前研究發現牛奶及優酪乳對於大腸癌可能有預防的效果。本研究目的為評估原料乳或以不同菌株發酵之優酪乳是否具有預防大腸癌發展的功效。利用化學致癌劑誘發的大腸癌動物模式，以蒸餾水(負控制組)、化學預防劑Piroxicam(正控制組)及優酪乳製造過程中的原料乳、基礎優酪乳(Streptococcus thermophilus及Lactobacillus bulgaricus)、含A菌優酪乳(S. thermophilus、L. bulgaricus和L. acidophilus)、含B菌優酪乳(S. thermophilus、L. bulgaricus和Bifidobacterium lactis)與含A、B菌優酪乳(S. thermophilus、L. bulgaricus、L. acidophilus和B. lactis)對F344大鼠施行管餵，在實驗飲食介入一週後以腹腔注射給予1,2-Dimethylhydrazine (DMH)誘發大腸癌，十週後犧牲大鼠。取其盲腸內容物檢測pH值及β-glucuronidase活性；大腸檢測異常腺窩病灶(Aberrant crypt feci, ACF)、黏液素分泌型態，而大腸黏膜分析發炎性蛋白第二型環氧合酶、誘導型一氧化氮合成酶表現量；並測其血液中免疫球蛋白A濃度。盲腸內容物之pH值及β-glucuronidase活性在各組間都無顯著差異。正控制組、原料乳組、基礎發酵乳組、含A菌優酪乳組及同時含A、B菌優酪乳組其大腸之ACF及異常腺窩數顯著低於負控制組，且基礎優酪乳組、含A菌優酪乳組及同時含A、B菌優酪乳組遠端大腸分泌sialomucin之ACF數顯著低於負控制組，然而黏液素缺乏病灶在各組間都無顯著差異。含B菌優酪乳組及同時含A、B菌優酪乳組近端結腸COX-2蛋白質表現顯著高於負控制組。所有的優酪乳組別血清免疫球蛋白A濃度顯著低於負控制組。本研究顯示餵食基礎優酪乳、含A菌優酪乳及同時含A、B菌優酪乳連續十週對於大腸癌發展早期指標具顯著抑制效果，推測是藉由抑制大腸癌形成過程黏液素的變化，而達到預防大腸癌的效果。
並列摘要
Malignancy is the first leading cause of death in Taiwan. Colorectal cancer, the third cause of cancer death in Taiwan, is the form of cancer most associated with diet. Yogurt is produced based on milk and fermented by probiotics. Previous study showed that milk and yogurt could prevent colorectal cancer. The purpose of this study was to assess the preventive effect of milk and yogurts fermented by various probiotics on the development of colorectal cancer. F344 rats were fed distilled water (negative control), piroxicam (positive control), milk, bsal yogurt (Streptococcus thermophilus and Lactobacillus bulgaricus), yogurt A (S. thermophilus, L. bulgaricus and L. acidophilus), yogurt B (S. thermophilus, L. bulgaricus and Bifidobacterium lactis) or yogurt AB (S. thermophilus, L. bulgaricus, L. acidophilus and B. lactis). After one week of feeding, rats were injected intraperitoneally with 1,2-dimethylhydrazine to induce colon carcinogenesis. After 10 weeks of feeding, rats were sacrificed. The cecal contents were examined for pH and β-glucuronidase activity; the colons were examined for aberrant crypt foci (ACF), mucin production, and the colonic mucosa for pro-inflammatory cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) protein expression; the blood were were examined for imunoglobulin A (Ig A) levels. The results showed that there were no significant differences in cecal pH and β-glucuronidase activity among groups. Postive control, milk, basal yogurt, yogurt A and yogurt AB significantly reduced the numbers of ACF and aberrant crypts in the colon as compared to negative control. Basal yogurt, yogurt A and yogurt AB significantly reduced the number of sialomucin-producing ACF in the distal colon as compared to negative control. There were no significant differences in mucin-depleted foci (MDF) number among groups. Yogurt B and AB significantly increased the COX-2 protein expression of the proximal colon as compared to negative control. All yogurt groups significantly reduced the plasma Ig A levels as compared to negative control. This study showed that basal yogurt and yogurt A and yogurt AB significantly inhibited the early markers of colorectal cancer after 10-week feeding, suggesting that these yogurts may inhibit colon carcinogenesis via mucin modification.