癌症患者血中微量元素与氧化应激的相关分析

背景:肿瘤的发生与发展是多因素作用的结果。肿瘤的早期诊断、疗效监测、预后评价至今较难。研究肿瘤发生与发展机制或肿瘤患者血液成分、组织分布的变化情况可为肿瘤患者的康复提供理论依据。目的:研究癌症患者血清中某些微量元素水平和过氧化-抗氧化系统的变化情况。设计:对照观察实验。单位:绵阳市中心医院检验科。对象:选择1999-09/2000-12四川自贡第三人民医院、四川宜宾第一人民医院和四川内江市隆昌县人民医院就诊的癌症患者111例,其中肝癌21例,胃癌16例,结肠直肠癌15例,乳腺癌11例,肺癌13例,食道癌13例,脑癌7例,其他癌种15例。同期健康体检者36例,为对照组。方法:受试者空腹,用VACUTEINER真空采血管(普通管,美国BD公司)抽取静脉血液样品至少5mL,2.0～3.0h以3000r/min离心15min分离血清2.0～3.0mL,测定前置冰箱冰冻保存。谷胱苷肽测定采用二硫代二硝基苯甲酸比色法。黄嘌呤氧化酶测定采用黄嘌呤-硝基四唑蓝比色法。谷胱苷肽过氧化物酶测定采用二硝基苯甲酸比色法。丙二醛测定采用硫代巴比妥酸比色法。抗坏血酸、维生素E和总抗氧化力测定采用菲罗啉比色法。白蛋白测定采用溴甲酚紫法。转铁蛋白、铜蓝蛋白测定采用散射比浊法。硒、铜、锌、铁测定采用原子吸收分光光度法。主要观察指标:丙二醛(作脂质过氧化指标);微量元素铜、锌、铁、硒及其转运蛋白(铜蓝蛋白、白蛋白和转铁蛋白);抗氧化态标志物:黄嘌呤氧化酶、谷胱苷肽、谷胱苷肽过氧化物酶、维生素E、维生素C浓度和总抗氧化力水平。结果:癌症患者脂质过氧化水平(以丙二醛计)明显高于对照癌症组为(5.21±1.05)nmol/L,对照组为(4.04±0.68)nmol/L,P<0.001],总抗氧化力明显低于对照癌症组为(4.34±0.98)U/L,对照组为(5.87±0.93)U/L,P<0.001]。抗氧化标志物黄嘌呤氧化酶、谷胱苷肽、谷胱苷肽过氧化物酶、维生素E和维生素C无明显变化。癌症患者血清白蛋白浓度明显低于对照癌症组为(34.19±6.94)g/L,对照组为(42.34±4.89)g/L,P<0.001],血清铜蓝蛋白浓度明显高于对照组癌症组为(0.371±0.031)g/L,对照组为(0.346±0.026)g/L,P<0.05],血清转铁蛋白浓度未发现有所改变(P>0.05)。血清铜水平明显高于对照癌症组为(19.27±4.74)μmol/L,对照组为(14.92±2.71)μmol/L,P<0.001],血清硒水平明显低于对照组癌症组为(1.175±0.333)μmol/L,对照组为(1.413±0.446)μmol/L,P<0.001],但锌和铁水平无显著变化。癌症患者血中铜和丙二醛之间呈明显相关性(r=0.281,P=0.003),但对照组铜与丙二醛未发现相关性存在。另外,肝癌患者血清铁和丙二醛存在相关关系(r=0.680,P=0.001)。结论:癌症患者氧化应激和某些微量元素呈相关变化,然而其变化情况可因癌种、癌症分期以及癌症患者个因素的不同而有所差异。

Correlation between oxidative stress and trace elements in blood of patients with cancer

BACKGROUND: The occurrence and development of tumor may result from the reaction of a series of factors. Up to now, earlier detection, monitoring treatment, and prognosis assessment for tumor are very difficult. It can provide the theoretical foundation of rehabilitation and survival for cancer patients to study the mechanisms of occurrence and development of tumors, or investigate the changes of blood level and tissue distribution.OBJECTIVE: To investigate the changes of levels of some trace elements and serous prooxidant-antioxidant system of cancer patients.DESIGN: A controlled observation trialSETTING: Department of Laboratory Medicine, Mianyang CentralHospital.PARTICIPANTS: From September 1999 to December 2000,111 cancer patients were selected from the Third People's Hospital of Zigong, Yibin First People's Hospital of Sichuan Province, and Longchang County people's Hospital of Neijiang City, Sichuan Province.Of them, 21 cases were of liver cancer, 16 of gastric carcinoma, 15 of colorectal cancer, 11 of breast cancer, 13 of lung cancer, 13 of esophageal cancer, 7 of brain cancer and 15 of other cancers. At the same time; 36 control subjects were recruited from those who came to the hospital for health examination.METHODS :Blood samples of subjects after overnight fasting were pre pared by collecting venous blood in 5-mL Vacutainer tubes (Becton Dickinson, American). After 2-3 hours, the blood samples were centrifuged at 3 000 r/min for 15 minutes. 2.0 to 3.0 mL of serum was separated. The sera were stored in the refrigerator until analysis. Serum glutathione(GSH)level was determined by dithiobis-2-nitrobenzoic acid colorimetry. Xanthine oxidase (XOD) concentration was determined with xanthine-nitrotetrazole colorimetry. Glutahione oxidase (GSHPx) activity was determined with dinitrobenzoic acid colorimetry. Malondialdehyde(MDA) concentration in serum was measured with thiobarbituric acid reaction. Vitamin C (Vit C),vitamin E(Vit E) and total antioxidant power(TAOP) levels were measured with phenanthroline colorimetry. Albumin concentration was determined with bromcresol purple. Serum transferrin (Trf) and ceruloplasmin (CER)concentrations were determined with immunonephelometry. The concentrations of Cu, Zn, Fe, and Se were measured with flame atomic absorption spectroscopy.MAIN OUTCOME MEASURES: MDA (as lipid peroxidation marker),trace elements copper, zinc, iron, and selenium and their transport proteins (albumin, transferrin and ceruloplasmin); antioxidation status markers: the concentrations of XOD, GSH, GSHPx, vitamin C, and vitamin E, and total antioxidant power levels.RESULTS: It was shown that lipid peroxidation ( measured as MDA)was significantly higher in cancer patients than in healthy controls (5.21±1.05) nmol/L vs (4.04±0.68) nmol/L,P ＜ 0.001], and the TAOP level was significantly decreased in cancer patients than in the health controls(4.34±0.980) U/L vs (5.87±0.93) U/L,P ＜ 0.001]. There were not obvious changes of antioxidation components (XOD, GSH, GSHPx, vitamin C,and vitamin E). Serum albumin concentration was found to be significantly lower in the cancer patients than in the health controls (34.19±6.94)g/L vs (42.34±4.89) g/L ,P ＜ 0.001], and serum ceruloplasmin concentration was found to be significantly higher in the cancer patients than in the health controls (0.371 ±0.031) g/L vs (0.346±0.026) g/L,P ＜ 0.05] butserum transferrin concentration remained unaltered (P ＞ 0.05). As com pared with the healthy controls, serum copper level was significantly increased(19.27±4.74) μmol/L vs (14.29±2.71) μmol/L, P ＜ 0.001], serum selenium levels was significantly decreased(1.175±0.333 0 μmol/L vs (1.413±0.446) μmol/L,P ＜ 0.001)]. However, the concentrations of zinc and iron remained unchanged. Correlation was observed between copper and MDA levels (r=0.281, P=0.003) in the cancer patients but not in the healthy controls. Moreover, a correlation was also observed between serum iron and MDA levels in the patients with liver cancer (r=0.680,P=0.001).CONCLUSION: The presence of an association between oxidative stress and some trace elements was found in cancer patients; however, the results are possibly inconsisteut because of different cancer types, cancer grades,or other characteristics of the patients engaged in the test.