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  • 學位論文

維生素 B-6 補充對切除肝腫瘤後之肝癌患者的血漿同半胱胺酸濃度及發炎反應之影響

The effect of vitamin B-6 supplementation on plasma homocysteine concentration and inflammatory responses in patients with hepatocellular carcinoma after tumor resection

指導教授 : 黃怡嘉

摘要


過去研究指出肝癌患者血漿磷酸比哆醛(維生素 B-6 的輔酶型式)濃度顯著低於健康受試者,但同半胱胺酸濃度顯著高於健康受試者。磷酸比哆醛雖然擔任同半胱胺酸轉硫作用以及發炎反應過程中的輔酶,但並不清楚若給予肝癌患者補充維生素 B-6 是否會降低其血漿同半胱胺酸濃度或改善發炎反應;此外同半胱胺酸與發炎反應的相關性也值得進一步確認。本研究是評估接受肝腫瘤切除術後之肝癌患者,補充維生素 B-6 後對其血漿同半胱胺酸及發炎反應之影響;此外,同半胱胺酸濃度與發炎反應之相關性也一併探討。於臺中榮民總醫院一般外科招募第一、二期接受肝腫瘤切除後之肝癌患者,隨機分派至維生素 B-6 組(n = 18, 50 mg/day)或是安慰組(n = 19),共介入 12 週。收集受試者第 0、4、8 及 12 週時的空腹血液進行生化值分析。維生素 B-6 組的同半胱胺酸濃度在介入第 4 週後顯著下降且持續維持到第 12 週,但安慰組的同半胱胺酸濃度則無顯著變化。維生素 B-6 及安慰組的高敏感度 C-反應蛋白及高敏感度介白素-6 皆分別在介入第 4 週及第 12 週後顯著低於介入前。以多重回歸模式調整年齡、性別、抽菸及喝酒習慣、介入前的肝功能指標(麩胺酸丙酮酸轉胺酶)、肝癌期別、有無肝炎以及肝硬化的干擾因子後,給予維生素 B-6 介入後會顯著降低同半胱胺酸濃度(β = -1.85, standard error = 0.78, p = 0.03),但對發炎指標(高敏感度 C-反應蛋白、介白素-6、腫瘤壞死因子-α)沒有顯著影響。另外同半胱胺酸濃度的變化量與發炎反應指標濃度變化量也無顯著的相關性。肝癌患者於腫瘤切除後接受維生素 B-6 補充可以顯著的降低血漿同半胱胺酸濃度,但對降低發炎指標則無顯著的效益。此外,同半胱胺酸的濃度變化與發炎反應也無顯著相關性。

並列摘要


Patients with hepatocellular carcinoma (HCC) have been observed to have lower plasma pyridoxal 5’-phosphate (PLP, the coenzyme form of vitamin B-6) and higher homocysteine concentrations when compared to those of healthy participants. Pyridoxal 5’-phosphate is an essential coenzyme in the transulfuration pathway of homocysteine metabolism and inflammatory response. However, it is not clear whether vitamin B-6 supplementation had effects on reducing plasma homocysteine concentration or inflammatory response in patients with HCC. It is also worth investigating the association between homocysteine and inflammatory response. The purpose of this study was to investigate whether vitamin B-6 supplementation had a significant effect on plasma homocysteine and inflammatory response in HCC patients after tumor resection. In addition, the association between plasma homocysteine level and inflammatory response was assessed. We recruited HCC patients with stage I or II after tumor resection at the division of general surgery of Taichung Veterans General Hospital. Subjects were randomly assigned to either the vitamin B-6 group (n = 18, 50 mg/day) or the placebo group (n = 19) for 12 weeks. Fasting blood samples were collected and measured at the 0, 4th, 8th and12th week. Plasma homocysteine concentration in the vitamin B-6 group was significantly reduced at week 4 and remained stable throughout the intervention period while there was no significant change in the placebo group. High sensitivity C-reactive protein and high sensitivity interleukin-6 were significantly decreased at week 4 and week 12 when compared to week 0 in both groups. Vitamin B-6 supplementation significantly reduced plasma homocysteine (β = -1.85, standard error = 0.78, p = 0.03), but had no significant effect on the changes of inflammatory markers (high sensitivity C-reactive protein, interleukin-6 and tumor necrosis factor-α) after adjusting for age, gender, smoking and drinking habits, the baseline level of alanine aminotransferase, HCC stage, hepatitis and cirrhosis by using multiple linear regression analysis. Moreover, there was no significant association between plasma homocysteine and the change of inflammatory markers. Vitamin B-6 supplementation could significantly reduce plasma homocysteine concentration, which could not further reduce inflammatory markers in patients with HCC after tumor resection.

參考文獻


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