米麩油非皂化物對DMH/DSS誘發鼠大腸癌病變之預防效果

本研究藉由1,2-dimethylhydrazine (DMH)/dextran sodium sulfate (DSS) 合併誘發模式，探討給予大鼠餵食米麩油非皂化物 (unsaponifiable matter obtained from rice bran oil, UM) 對大腸癌病變之預防效果，及探討米麩油非皂化物能否調控體內抗氧化狀態及發炎反應而有助於預防大腸癌病變。將Fisher 344大鼠分為五組並全程給予實驗飼料。其中空白組 (Blank, B) 未誘發大腸癌並給予AIN-93G標準配方飼料；其餘四組以DMH/DSS模式誘發大腸癌，分別為給予AIN-93G飼料的控制組 (Control, C)；AIN-93G飼料中含有0.8% γ-oryzanol之oryzanol組 (Oryzanol, O)；AIN-93G飼料中含有0.4% 及0.8% 米麩油非皂化物的低劑量非皂化物組 (Low dose of UM, L) 及高劑量非皂化物組 (High dose of UM, H)。實驗期第一週時給予腹腔注射三劑DMH (40 mg/kg body weight)，接著給予連續一週含1% DSS的飲水以誘發大腸癌，並於給予DSS後以疾病活性指標 (disease activity index, DAI) 分數觀察大腸發炎嚴重程度。實驗期16週後予以犧牲，取其大腸、肝臟及血液進行分析。以DMH/DSS誘發之組別分析其大腸組織病理形態，包含大腸腫瘤、異常腺窩 (aberrant crypt, AC)、異常腺窩病灶 (aberrant crypt foci, ACF)、微腺瘤 (microadenoma)、ACF之黏液素 (mucin) 形態及黏液素缺乏病灶 (mucin depleted foci, MDF)；所有組別皆分析血漿中thiobarbituric acid-reactive substances (TBARS) 濃度與總抗氧化能力 (total antioxidant capacity)；大腸及肝臟 superoxide dismutase (SOD)、catalase (CAT) 及glutathione peroxidase (GPx) 活性與TBARS 濃度；大腸黏膜促發炎酵素cyclooxygenase-2 (COX-2) 及inducible nitric oxide synthase (iNOS) 蛋白質表現量。結果顯示給予米麩油非皂化物能降低DAI分數，改善大鼠產生血便或腹瀉等大腸發炎急性症狀；減少大鼠大腸癌病變，如AC、ACF、MDF及微腺瘤，並調節黏液素分泌形態，具抑制大腸癌病變及延緩病程進展之作用。給予米麩油非皂化物亦能提升抗氧化酵素的活性，尤其改善大腸CAT、GPx及SOD降低之現象，並減少氧化壓力，尤其改善大腸TBARS異常上升，亦能提升體內總抗氧化能力促使大腸癌大鼠回復體內抗氧化狀態；同時降低因誘發大腸癌上升之COX-2表現，調節體內發炎反應。本研究顯示米麩油非皂化物有助於減少大腸癌病變及其惡化程度，進而預防大腸癌進展。

關鍵字

大腸癌；米麩油；非皂化物；異常腺窩病灶；黏液素缺乏病灶；抗氧化；第二型環氧酵素

並列摘要

This study investigated the effects of unsaponifiable matter (UM) obtained from rice bran oil (RBO) on colon carcinogenesis in rats induced by 1,2-dimethylhydrazine (DMH)/dextran sodium sulfate (DSS). F344 rats were fed AIN-93G-based diets and divided into five groups: group B, AIN-93G (blank); group C, AIN-93G (control); group O, AIN-93G containing 0.8% γ-oryzanol; group L, AIN-93G containing 0.4% UM (low dose of UM); group H, AIN-93G containing 0.8% UM (high dose of UM). All rats except those in group B were given three injections of DMH (40 mg/kg body weight) in a week followed by free access to drinking water containing 1% DSS for a week to induce colon carcinogenesis, and the severity of the colitis was assessed using disease activity index (DAI). After 16 weeks, DMH/DSS-treated rats were sacrificed and their colons were removed to examine for colon tumors and preneoplastic lesions, such as aberrant crypts (AC), aberrant crypt foci (ACF), mucin-depleted foci (MDF) and microadenoma. The mucin morphology of ACF was also assessed. All rats were examined for total antioxidant capacity and thiobarbituric acid-reactive substances (TBARS) level in plasma. Activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and TBARS level were measured in colons and livers. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions in colonic mucosa were also assessed. The results showed that UM significantly reduced the numbers of AC, ACF, MDF, microadenoma and the incidence of MDF. Furthermore, UM suppressed the alteration of mucin in ACF. DAI score, total antioxidant capacity, activities of antioxidative enzymes, TBARS level and COX-2 expression were superior among the UM groups, which might contribute to the potential of UM with respect to delaying colon carcinogenesis.

並列關鍵字

Colon cancer ； Rice bran oil (RBO) ； Unsaponifiable matter (UM) ； Aberrant crypt foci (ACF) ； Mucin-depleted foci (MDF) ； Antioxidation ； Cyclooxygenase-2 (COX-2)

參考文獻

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國際替代計量

米麩油非皂化物對DMH/DSS誘發鼠大腸癌病變之預防效果

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