不同形式硒对二乙基亚硝胺致大鼠肝癌细胞因子和血管生成调节因子的影响

Effects of different forms of selenium on the cytokines and angiogenesis promoters of diethylnitrosamine-induced hepatocarcinoma rats

雄性SD大鼠153只。体质量100—120g，随机分为4组。阴性对照组、模型组日粮中添加亚硒酸钠至硒含量为0．1mg·kg^-1；富硒麦芽组（SEM）、亚硒酸钠组（SS）日粮中分别添加富硒麦芽和亚硒酸钠至硒含量达3．0mg·kg^-1。在模型组、SEM组、SS组饮水中添加二乙基亚硝胺（DEN，100mg·L^-1）诱癌，连续16周。阴性对照组始终以普通灭菌水自由饮用。每4周各组鼠眼眶采血5只，18周末采血，处死所有大鼠。结果发现，与同期模型组相比，SEM组血清白介素2（IL-2）显著升高（第8、12周除外），胰岛素样生长因子Ⅱ（IGF-Ⅱ）（第4、8周除外）和一氧化氮合酶（NOS）含量，以及肝肿瘤组织血管内皮生长因子（VEGF）阳性表达均显著降低；绝大部分时间内，SS组的IGF—Ⅱ、一氧化氮（NO）、NOS和VEGF水平接近甚至高于同期模型组，仅于试验后期见IL-2升高和肿瘤坏死因子α（TNFα）下降。说明富硒麦芽通过促进肝癌大鼠非特异性免疫功能，抑制肿瘤血管生成因子活性，发挥其抗癌作用；亚硒酸钠对细胞因子活性的调节作用弱于富硒麦芽，对肿瘤血管生成因子无明显抑制作用。

Total 153 SD rats weighing 100 - 120 g were randomly divided into 4 groups. Animals in the negative control group and positive control group were fed the diets with 0.1 mg· kg^-1 selenium （from sodium selenite）, respectively. The animals in SEM group and SS group were fed the diets with 3.0 mg· kg^-1 selenium from Se-enriched malt （SEM） or sodium selenite （SS）, respectively. Animals in positive control group, SEM group and SS group were induced hepatocarcinoma by diethylnitrosamine diluted in the sterilized water （ 100 mg · L^-1） at the dose of 10 mg· kg^-1 body weight every day for 16 weeks, then drunk with sterilized water for another 2 more weeks. Rats in the negative control group were drunk normal water during the whole experimental time. Subsequently, blood samples of five animals in each group were taken from orbit in every 4 weeks. At the end of the 18th week, all the rats were killed by cervical decapitation after blood samples were taken. The results indicated that the levels of TNFα, IGF Ⅱ （except that at the 4th and 8th week）, NOS and the expression of vascular endothelial growth factor （VEGF） of the tumor in SEM-treated group were significantly decreased, simultaneously, the contents of IL- 2 （except that at the 8th and 12th week） in the serum were significantly increased as compared with those of the positive control group at the same sampling time. However, in the most sampling time, the levels of IGF -Ⅱ, NO, NOS and VEGF in SS-treated group were high or near to that of the positive control group at the same sampling time. And the levels of TNFα and IL - 2 in SS-treated group were decreased and increased, respectively, as compared with those of the positive control group at the end of the same sampling time. In conclusion, the function of So-enriched malt in promoting the nonspecific immune function and inhibiting the angiogenesis promoters was better than that of sodium selenite. Sodium selenite has no significant effect on the angiogenesis promoters during the process of hepatocarcinogenesis.