肝癌患者腫瘤切除前後其穀胱甘肽及抗氧化酵素活性與氧化壓力變化之關係

The associations of glutathione and antioxidant enzyme activities with oxidative stress changes before and after tumor resection in patients with hepatocellular carcinoma

陳心爰(Sin-Yuan Chen)

指導教授 ： 黃怡嘉

中山醫學大學/健康管理學院/營養學研究所/碩士(2016年)

摘要

肝臟腫瘤患者可能因腫瘤組織存在會影響體內氧化壓力、穀胱甘肽濃度以及抗氧化酵素活性，但是目前有關肝臟腫瘤切除後的氧化壓力及抗氧化能力與腫瘤切除前的變化則尚未清楚。此外肝臟腫瘤組織中的穀胱甘肽濃度與正常組織的差異也尚未被詳細檢視。本研究目的是探討第一、二期肝癌患者在切除腫瘤前後其氧化壓力與血清穀胱甘肽濃度及抗氧化能力變化之關係；以及比較肝臟腫瘤組織及鄰近周邊正常組織的穀胱甘肽濃度差異。於臺中榮民總醫院一般外科招募 61 位欲接受肝臟腫瘤切除受試者。在受試者腫瘤切除前和腫瘤切除後二星期抽取空腹血液分析氧化壓力指標（丙二醛、氧化型低密度脂蛋白）、總抗氧化能力、穀胱甘肽濃度、超氧歧化酶活性、穀胱甘肽相關酵素活性，以及收集肝臟腫瘤組織及其鄰近周邊正常組織分析穀胱甘肽濃度。結果顯示受試者腫瘤切除後的氧化壓力指標（丙二醛、氧化型低密度脂蛋白）較腫瘤切除前顯著降低。腫瘤切除後的總抗氧化能力、還原型及氧化型穀胱甘肽濃度、穀胱甘肽還原酶及超氧化物岐化酶活性皆較腫瘤切除前顯著增加，但穀胱甘肽硫轉移酶活性則是顯著下降。腫瘤組織的穀胱甘肽濃度顯著高於鄰近周邊正常組織的濃度。以 Partial Spearman correlation 調整相關干擾因子後，腫瘤切除前的血清（rs = 0.4, p = 0.01）及腫瘤組織（rs = 0.34, p = 0.03）的穀胱甘肽濃度皆與腫瘤切除前血漿丙二醛濃度呈現顯著正相關。肝癌患者於肝臟腫瘤切除後的氧化壓力的確較腫瘤切除前顯著下降，而總抗氧化能力、穀胱甘肽及抗氧化酵素活性則顯著增加。另外，肝臟腫瘤組織的穀胱甘肽濃度顯著高於鄰近周邊正常肝臟組織，且與氧化壓力有相關。

關鍵字

肝癌 ； 腫瘤切除 ； 穀胱甘肽氧化壓力 ； 抗氧化酵素活性

並列摘要

Patients with hepatocellular carcinoma (HCC) might have increased oxidative stress but decreased glutathione level and antioxidant enzyme activities due to the presence of tumor. However, it is not clear the changes of oxidative stress and antioxidant capacities before and after tumor resection in patients with HCC. In addition, the difference in glutathione level between liver tumor tissue and adjacent normal tissue has not been extensively studied. The purpose of this study was to evaluate the associations of changes of glutathione and antioxidant enzyme activities with the change of oxidative stress before and after tumor resection in patients with stage 1 or 2 HCC, and additionally compared the difference in glutathione level between liver tumor tissue and adjacent normal tissue. We recruited 61 patients with stage 1 or 2 HCC from the division of general surgery of Taichung Veterans General Hospital, Taiwan. Fasting blood samples were drawn on the day before and two weeks after the tumor resection to measure oxidative stress indicator (malondialdehyde, MDA; oxidized low-density lipoprotein, ox-LDL), glutathione, activities of superoxide dismutase (SOD) and glutathione -dependent enzymes. Tumor and adjacent normal liver tissues were collected at the day of receiving tumor resection. Results showed that patients had significantly lower levels of oxidative stress indicator and glutathione S-transferase (GST) activity, but had significantly higher levels of trolox equivalent antioxidant capacity (TEAC), reduced and oxidized glutathione, activities of glutathione reductase (GR) and SOD after tumor resection than did before tumor resection. There was a significantly higher glutathione level in liver tumor tissue when compared to adjacent normal liver tissue. Serum glutathione level before tumor resection (rs = 0.4, p = 0.01) and glutathione level in liver tumor tissue (rs = 0.34, p = 0.03) were positively associated with the MDA level before tumor resection. Patients had significantly decreased oxidative stress, but had significantly higher TEAC, glutathione status, and antioxidant enzyme activities after tumor resection. In addition, glutathione level in liver tumor tissue was significantly higher than did in adjacent normal liver tissue, and had a significant association with oxidative stress.

並列關鍵字

hepatocellular carcinoma ； tumor resection ； glutathione ； oxidative stress ； antioxidant enzyme activities

參考文獻

Abou Ghalia AH, & Fouad IM. (2000). Glutathione and its metabolizing enzymes in patients with different benign and malignant diseases. Clin Biochem, 33(8), 657-662.

Arnao MB, Cano A, Hernandez-Ruiz J, Garcia-Canovas F, & Acosta M. (1996). Inhibition by L-ascorbic acid and other antioxidants of the 2.2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) oxidation catalyzed by peroxidase: a new approach for determining total antioxidant status of foods. Anal Biochem, 236(2), 255-261.

Bakan N, Taysi S, Yilmaz O, Bakan E, Kuskay S, Uzun N, & Gundogdu M. (2003). Glutathione peroxidase, glutathione reductase, Cu-Zn superoxide dismutase activities, glutathione, nitric oxide, and malondialdehyde concentrations in serum of patients with chronic lymphocytic leukemia. Clin Chim Acta, 338(1-2), 143-149.

Beasley RP, Hwang LY, Lin CC, & Chien CS. (1981). Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet, 2(8256), 1129-1133.

Bianchi G, Bugianesi E, Ronchi M, Fabbri A, Zoli M, & Marchesini G. (1997). Glutathione kinetics in normal man and in patients with liver cirrhosis. J Hepatol, 26(3), 606-613.