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  • 學位論文

同半胱胺酸及維生素B-6與大腸直腸瘜肉受試者之抗氧化能力及代謝症候群之相關性

Homocysteine and vitamin B-6 in relation to the antioxidant capacities and metabolic syndrome in subjects with colorectal polyps

指導教授 : 黃怡嘉

摘要


本研究目的為探討同半胱胺酸及維生素B-6對於大腸直腸瘜肉患者的氧化壓力、抗氧化能力的影響,以及同半胱胺酸、代謝症候群與大腸直腸瘜肉三者之間的相關性。本研究在第一階段共募集了48位大腸直腸瘜肉患者(29位為腺瘤性瘜肉、19位為增生性瘜肉)及96位經年齡性別配對的健康受試者。分析其血液B-維生素(維生素B-6 [pyridoxal 5’-phosphate, PLP]、葉酸、及維生素B-12)營養狀況、血漿同半胱胺酸濃度,並計算其對於大腸直腸瘜肉的危險比(odds ratio, OR)及95% 信賴區間(confidence interval, CI)。結果發現,PLP、葉酸、及維生素B-12在兩組之間並無顯著差異,且對於大腸直腸瘜肉亦無顯著影響。在調整了相關影響因子後,同半胱胺酸顯著增加罹患大腸直腸瘜肉的危險(OR, 1.87, 95% CI, 1.13 - 3.08)。同半胱胺酸可能是大腸直腸瘜肉的獨立危險因子。 第二階段進一步探討同半胱胺酸與血漿PLP濃度是否會影響大腸直腸瘜肉患者的氧化壓力(脂質過氧化程度)及抗氧化能力(榖胱甘肽硫轉移酶及榖胱甘肽過氧化酶活性)。本階段共募集110位大腸直腸瘜肉患者(70位為腺瘤性瘜肉、40位為增生性瘜肉)與168位大腸直腸癌患者。檢測其血漿同半胱胺酸、半胱胺酸及PLP濃度,體內氧化壓力程度及抗氧化酵素活性。結果發現,在調整相關因子之後,血漿同半胱胺酸、半胱胺酸及PLP濃度對於體內氧化壓力程度及抗氧化酵素活性並無顯著影響。而只有半胱胺酸對於大腸直腸瘜肉患者之穀胱甘肽硫轉移酶及穀胱甘肽過氧化酶活性有顯著影響。因此推論在維生素B-6營養狀況充足下,對於大腸直腸瘜肉患者的抗氧化能力而言,半胱胺酸可能是比起同半胱胺酸更顯著的影響因子。 除了同半胱胺酸濃度之外,本研究亦觀察到53.6%的大腸直腸瘜肉受試者有代謝症候群,因此第三階段進一步比較110位大腸直腸瘜肉患者與135位健康受試者之間的同半胱胺酸濃度及代謝症候群相關項目的差異。大腸直腸瘜肉患者代謝症候群項目中,除三酸甘油酯之外,皆顯著高於健康對照組。同半胱胺酸與代謝症候群皆分別顯著增加大腸直腸瘜肉的危險性。若是將同半胱胺酸及代謝症候群一起探討對於大腸直腸瘜肉的影響時,調整相關影響因子後,僅代謝症候群仍然有顯著影響。因此,代謝症候群可能較同半胱胺酸是更重要的大腸直腸瘜肉獨立危險因子。

並列摘要


The purposes of this research were to investigate the effects of homocysteine and vitamin B-6 concentration on oxidative stress and antioxidant capacities in participants with colorectal polyps. Additionally, the relationships among homocysteine, metabolic syndrome and the risk of colorectal polyps were studied. The first part of this study, 48 participants with colorectal polyps (29 adenomatous polyps, 19 hyperplastic polyps) and 96 age- and sex-matched healthy controls were recruited. We measured hematological parameters, plasma pyridoxal 5’-phosphate (PLP), serum folate and vitamin B-12, and plasma homocysteine. Participants with colorectal polyps had significantly higher plasma homocysteine level when compared to the controls. B-vitamins had no significant effect on the risk of colorectal polyps. However, higher plasma homocysteine level significantly increased risk of colorectal polyps after adjusting for potential confounders (odds ratio = 1.87, 95% confidence interval = 1.13, 3.08). Plasma homocysteine was a strong predictor of the risk of colorectal polyps. We next investigated the association of plasma homocysteine, cysteine, and plasma PLP with oxidative stress indicators [i.e., malondialdehyde (MDA) and oxidized low density lipoprotein cholesterol (ox-LDL)] and antioxidant enzyme activities [i.e., glutathione peroxidase (GPx) and glutathione S-transferase (GST)] in patients with colorectal polyps or colorectal cancer. 110 participants with colorectal polyps (70 participants with adenomatous polyps, 40 participants with hyperplastic polyps) and 168 patients with colorectal cancer were recruited. No significant differences in plasma MDA, ox-LDL and GST activities were observed among the three groups. Plasma homocysteine, cysteine, PLP and GSH levels had no effects on oxidative stress indicators after adjusting for potential confounders. Only plasma cysteine significantly correlated with GPx and GST activities after adjusting for potential confounders in the colorectal polyps group. Cysteine rather than homocysteine is an important contributing factor in GPx and GST activities in participants with colorectal polyps when plasma PLP is adequate. Metabolic syndrome has been shown to be associated with the risk of colorectal polyps. We then investigated whether there was interaction between homocysteine and metabolism syndrome on the development of colorectal polyps. Metabolic syndrome and plasma homocysteine were individually significantly associated with the risk of colorectal polyps. However, when the association of metabolic syndrome and homocysteine with the risk of colorectal polyps was simultaneously considered, the association between homocysteine and the risk of colorectal polyps disappeared, but metabolic syndrome itself was still a significant risk factor for the development of colorectal polyps. Metabolic syndrome was a major contributing factor in relation to the risk of colorectal polyps independent of plasma homocysteine.

參考文獻


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