丁酸钠抑制二甲基肼诱发小鼠大肠癌的实验研究

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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 & AIM: In vitro studies have demonstrated that sodium butyrate can promote the differentiation of a variety of tumor cells, inhibit cell growth and induce apoptosis. In this study, intraperitoneal sodium butyrate was administered to mice to observe the preventive effect of sodium butyrate on colorectal cancer induced by dimethylhydrazine (DMH) in mice. Methods: Kunming mice were selected as experimental group. The model group was given subcutaneously with DMH30mg / kg once a week for 11 weeks. Experimental groups were treated with 1.25 × 10-3mol / kg, 2.5 × 10-3mol / kg sodium butyrate solution, rectally, once a day for 24 weeks. Mice were sacrificed in 3 stages at 12th week, 18th week and 24th week after administration respectively. The incidence of tumor and the general state, body weight gain, liver and kidney function, pathological changes of liver, kidney, lung and pancreas in 2.5 × 10-3mol / kg sodium butyrate enema group were observed. Results: At 12 weeks of experiment, no tumor occurred in each group of mice. At 18 weeks, the incidence of tumor in model group was 58.3% (7/12). The incidence of tumor in 1.25 × 10-3 mol / kg sodium butyrate group was 25.0 (3/12). The incidence of tumor in sodium butyrate group was 0 (0/12) in 2.5 × 10-3mol / kg group (P <0.01). The results of 24 weeks in experimental group, model group The incidence of tumor in mice was 95.0% (19/20), incidence rate of tumor was 45.0% (9/20) in 1.25 × 10-3mol / kg sodium butyrate group, tumor incidence rate in 2.5 × 10-3mol / kg sodium butyrate group 15.0% (3/20), there was a significant difference among the groups (P <0.01). Pure 2.5 × 10-3mol / kg sodium butyrate enema group and saline control group were not found in the tumor. Simple 2.5 × 10-3mol / kg sodium butyrate enema group mice in general good condition, weight gain and liver and kidney function were not significantly different from the saline group (P> 0.05), liver, kidney, pancreas and other important dirty Pathological changes have not seen. CONCLUSION: Sodium butyrate can inhibit the occurrence and development of colorectal cancer induced by DMH in mice with no obvious side effects.
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