丁酸钠抑制二甲基肼诱发小鼠大肠癌的实验研究  

Inhibitory Effect of Sodium Butyrate on 1,2-Dimethylhydrazine-induced Tumorigenesis of Colorectal Cancer in Mice

作　　者：刘成霞[1] 张尚忠[1] 张孝卫[2] 耿秀兰[2] 李铁军[2] 黄丽华[2] 王兵[2] 

机构地区：[1]山东大学齐鲁医院消化科,山东济南250012 [2]济南市医学科学研究所,山东济南250013

出　　处：《癌症》2005年第8期930-934,共5页Chinese Journal of Cancer

摘　　要：背景与目的:体外研究证实丁酸钠能促进多种肿瘤细胞分化,抑制细胞生长,诱导细胞凋亡。本研究给予小鼠直肠内灌注丁酸钠,旨在观察丁酸钠对二甲基肼(dimethylhydrazine,DMH)诱发的昆明种小鼠大肠癌的预防作用。方法:选择昆明种小鼠为实验对象,模型组以DMH30mg/kg,皮下注射,每周一次,连续给药11周。实验组分别以1.25×10-3mol/kg、2.5×10-3mol/kg丁酸钠溶液,直肠灌注,每天一次,连续24周。分别于给药后第12周、18周和24周分3个阶段处死小鼠。观察肿瘤的发生率,以及2.5×10-3mol/kg丁酸钠灌肠组小鼠的一般状态、体重增长、肝肾功能、以及肝、肾、肺、胰腺等病理变化。结果:实验12周各组小鼠未见肿瘤发生;18周时,模型组小鼠肿瘤发生率为58.3%(7/12),1.25×10-3mol/kg丁酸钠组肿瘤发生率为25.0%(3/12),2.5×10-3mol/kg丁酸钠组肿瘤发生率为0(0/12),各组相比差异有显著性(P<0.01);实验24周结果,模型组小鼠肿瘤发生率为95.0%(19/20),1.25×10-3mol/kg丁酸钠组肿瘤发生率45.0%(9/20),2.5×10-3mol/kg丁酸钠组肿瘤发生率为15.0%(3/20),各组间有显著性差异(P<0.01)。单纯2.5×10-3mol/kg丁酸钠灌肠组和生理盐水对照组均未发现肿瘤。单纯2.5×10-3mol/kg丁酸钠灌肠组小鼠一般状态良好,体重增长及肝、肾功能均与生理盐水灌肠组无显著性差异(P>0.05),肝脏、肾脏、胰腺等重要脏器未见病理性改变。结论:丁酸钠能够抑制DMH诱发的实验性小鼠大肠癌的发生和发展,并且无明显毒副作用发生。BACKGROUND ＆ OBJECTIVE： In vitro studies proved that sodium butyrate （NAB） could stimulate cell differentiation, inhibit cell proliferation, and induce cell apoptosis in various tumors. This study was to evaluate the preventive effects of coloclysis of NaB on 1,2-dimethylhydrazine（DMH）-induced tumorigenesis of colorectal cancer in mice. METHODS, The mice of Kunming species were divided into 5 groups and received relevant treatments：DMH alone group （with subcutaneous injection of 30 mg/kg of DMH weekly for 11 weeks）, control （normal saline, NS） group, DMH plus low dose of NaB （1.25 mol/kg, 24-week coloclysis） group, DMH plus high dose of NaB （2.5 mol/kg, 24-week coloclysis） group, and high dose of NaB group. The mice were killed in batches at the 12^th, 18^th, and 24^th weeks of carcinoma induction separately. The incidence of colorectal tumor in each group was observed. Meanwhile, the general condition, body weight increasing, liver and renal functions, and pathologic changes of liver,kidney, lungs, and pancreas of the mice in DMH plus high dose of NaB group were also observed. RESULTS： No tumor was observed at the 12^th week in each group. At the 18^th week, the tumor incidence was significantly higher in DMH alone group and DMH plus low dose of NaB group than in DMH plus high dose of NaB group （58.3%, and 25.0% vs. 0, P〈0.01）. Atthe 24^th week, the tumor incidence was 95.0% in DMH alone group, 45.0% in DMH plus low dose of NaB group, and 15.0% in DMH plus high dose of NaB group; the differences among the 3 groups were significant （P=0.01, P〈0.01）. No tumor was observed in control group and high dose of NaB group.There was no difference in the general condition, body weight increasing,and liver and renal functions of the mice between control group and high dose of NaB group （P〉 0.05）; no pathologic changes in liver, kidney,lungs, and pancreas were observed in the mice in high dose of NaB group.CONCLUSION： NaB could inhibit DMH-induced tumorigenesis of colorecta

关 键 词：丁酸钠/拮抗剂和抑制剂 二甲基肼/毒性 大肠肿瘤/化学诱导 大肠肿瘤/预防和控制 小鼠 

分 类 号：R735.34[医药卫生—肿瘤]