长期注射成纤维细胞生长因子21对二乙基亚硝胺诱发肝癌的预防作用  

Long-term administration of fibroblast growth factor 21 prevents DEN-induced hepatocarcinogenesis

作　　者：李德山[1] 张瑛杰[1] 徐鹏飞[1] 袁清艳 任桂萍[1] 刘铭瑶[1] 刘芝航 

机构地区：[1]东北农业大学生命科学学院,哈尔滨150030

出　　处：《东北农业大学学报》2016年第3期17-22,30,共7页Journal of Northeast Agricultural University

基　　金：国家自然基金东北农业大学生物学理科基地科研训练及科研能力提高项目(J1210069/J0116)

摘　　要：研究成纤维细胞生长因子21(FGF21)对二乙基亚硝胺(DEN)诱导肝癌模型的预防作用及机制。健康雄性wistar大鼠随机分3组:FGF21组,模型对照组及正常对照组。FGF21组大鼠每天注射一次FGF21,注射20周。2周后,FGF21组大鼠和模型组大鼠同时每3 d注射一次DEN,直至试验结束。给药结束后,取各组大鼠血清样本测定肝功,统计各组大鼠肝癌发生率,比较各组大鼠肝脏内氧化应激水平。结果表明,FGF21治疗组肝功显著低于模型对照组,接近正常水平。通过分析各组大鼠肝脏变化发现,FGF21治疗组大鼠肝癌发生率为18.1%,而注射生理盐水的模型对照组肝癌发生率为60.0%。FGF21治疗组肝脏内的活性氧(ROS)、丙二醛(MDA)含量显著低于模型对照组,接近正常对照组;FGF21治疗组肝脏内超氧化物歧化酶(SOD)活性与正常对照组持平,显著高于模型对照组。Real-time PCR结果显示,FGF21治疗组肝脏的抗氧化酶基因(G6pdh,GCL-c,Gpx-1,Sod2)表达水平显著高于模型对照组。结果表明,长期注射FGF21可通过抑制肝脏内氧化应激水平预防DEN诱导的肝癌。This paper was to evaluate the preventive effect of fibroblast growth factor 21 （FGF21） on diethylnitrosamine （DEN） induced hepatocarcinogenesis in rats and to provide mechanistic insights into its preventive effect. Healthy male wistar rats were randomized into 3 groups： FGF21 group, model control and normal control. Rats were administered with FGF21 once daily for 20 weeks. Two weeks later, the rats were simultaneously administered with DEN every three days until the end of the experiment. At the end of the treatment, blood samples were collected, and liver function was measured. Then the tumor incidence in each liver tissue was analyzed. Besides, we also compared the oxidative stress levels of the livers in each arouD. The results showed that the liver founction of the model control group was significantly higher than FGF21 treatment group, which was closed to the normal control group. By analyzing the changes in the livers, found that the hepatoma incidence of the rats treated with FGF21 was 18.1%, while the incidence of the rats treated with saline was 60.0%. The treatment also found that the ROS production and MDA content were significantly increased and the activity of the SOD was significantly decreased compared with normal group and FGF21 group, whereas MDA content and the activity of SOD between the normal group and FGF21 group were not statistically difference. The realtime PCR showed that the expression of the antioxidant genes （G6pdh, GCL-c, Gpx-1, Sod2） in model control group was significantly up-regulated compared with normal control group and FGF21 group, whereas expression levels of the antioxidant genes in the FGF21 group were significantly improved compared to the model control group. To summary, long-term admini- stration of FGF21 could prevent DEN-induced hepatocarcinogenesis via suppressing oxidative stress.

关 键 词：成纤维细胞生长因子21 二乙基亚硝胺 肝癌 氧化应激 

分 类 号：R575[医药卫生—消化系统] Q816[医药卫生—内科学]