维生素E和硒缺乏促进大鼠食管肿瘤发生及氧化应激机制的研究  

Effect of vitamin E and selenium deficiency on esophageal tumorigenesis and its oxidative stress mechanism

作　　者：杨辉[1] 李永宁[2] 方瑾[2] 贾旭东[2] 李宁 

机构地区：[1]中国疾病预防控制中心营养与食品安全所,北京100021 [2]国家食品安全风险评估中心

出　　处：《卫生研究》2013年第1期23-30,共8页Journal of Hygiene Research

基　　金：国家自然科学基金资助项目(No.30872110)

摘　　要：目的探讨维生素E(VE)和硒(Se)营养缺乏对食管肿瘤发生的影响及其氧化应激机制。方法 110只雄性F344大鼠随机分为3组:VE/Se缺乏组,VE/Se正常组和溶剂对照组。VE/Se缺乏组和VE/Se正常组动物皮下注射N-甲基苄基亚硝胺(NMBzA)染毒,染毒剂量为0.35 mg/kg BW,每周3次,连续5周。溶剂对照组动物皮下注射等体积的20%二甲基亚砜(DMSO)。VE/Se缺乏组给予低VE/Se饲料(VE 46U/kg,Se 0.05mg/kg),VE/Se正常组、溶剂对照组给予正常饲料(VE 80U/kg,Se 0.15mg/kg)。在实验第25周解剖动物,进行食管肿瘤肉眼观察及病理检查。动物血浆VE水平采用高效液相色谱法检测,Se水平采用荧光法检测。食管组织中细胞增殖和DNA氧化损伤分别采用5-溴脱氧尿嘧啶(BrdU)和8羟基脱氧鸟苷(8-OH-dG)免疫组织化学法检测。动物血浆、食管及肝脏谷胱甘肽过氧化物酶(GPX)、谷胱甘肽转移酶(GST)活性采用试剂盒法检测。结果动物血浆VE和Se水平VE/Se缺乏组显著低于VE/Se正常组,VE/Se正常组略低于溶剂对照组。VE/Se缺乏组动物食管肉眼可见肿瘤发生率、平均肿瘤数量及病理损伤数量均显著高于VE/Se正常组(P<0.05);与VE/Se正常组相比,VE/Se缺乏组动物食管组织细胞增殖水平、8-OH-dG水平显著升高(P<0.05);动物血浆、食管及肝脏GPX和GST活性显著降低(P<0.05)。结论维生素E和硒缺乏能够加快细胞增殖,显著促进NMBzA诱发的大鼠食管肿瘤的发生,机体氧化应激、DNA氧化损伤在食管癌变过程中具有重要作用。Objective To explore the effect of vitamin E （VE） and selenium （Se） deficiency on esophageal tumorigenesis and its oxidative stress mechanism. Methods 110 male F344 rats were randomly divided into 3 groups： VE/Se deficient group （group A）, VE/Se normal group （group B） and control group （group C）. Animals in group Aand group B were subcutaneously injected with N-nitrosomethylbenzylamine （NMBzA） at the dosage of 0.35 mg/kg BW, 3 times per week for 5 weeks. Control group was given the solvent 20% DMSO as negative control. Animals in group A were fed with low-VE/Se diet （46IU/kg VE, 0.05mg/kg Se）, animals in group B and C were fed with normal diet （80IU/kg VE, 0.15mg/kg Se）. Animals were sacrificed to perform macroscopic observation and pathologic inspection at the 25th week of the experiment. Plasma VE level was determined by high-performance liquid chromatography, and Se level was determined by fluorescence method. Cell proliferation and DNA damage in esophagus were detected through immunohistochemistry of BrdU and 8-OH-dG, respectively. Glutathione peroxidase （GPX） and glutathione transferase （GST） activities in plasma, esophagus and liver were analyzed by using test kits. Results VE/Se levels of group A were significantly lower than those of group B, the later were slightly lower than those of group C. Visible tumor incidence, tumor multiplicity and pathologic lesions in group A were all significantly more than those in group B. Comparing with group B, cell proliferation and 8-OH-dG levels were also significantly increased in group A. GPX and GST activities in plasma, esophagus and liver of group A were significantly higher than those of group B. Conclusion Vitamin E and selenium deficiency significantly promoted the NMBzA-induced esophageal tumorigenesis. Oxidative stress and DNA damage may be one of the critical routes by which NMBzA induces carcinogenesis in rat esophagus.

关 键 词：维生素E硒 营养缺乏食管癌 氧化应激 

分 类 号：Q566[生物学—生物化学] R735.1[医药卫生—肿瘤]