小檗碱对实验性大鼠结肠癌的防治作用及其与过氧化物增殖物激活受体γ表达的相关性  

Preventive and Curative Effects of Berberine on Experimental Colon Cancer in Rats and Its Relationship to Expression of Peroxisome Proliferator-activated Receptor γ

作　　者：吴柯[1] 何百成[1] 周岐新[1] 

机构地区：[1]重庆医科大学药学院药理教研室重庆市生物化学与分子药理学重点实验室,重庆400016

出　　处：《中国生物制品学杂志》2011年第8期952-956,共5页Chinese Journal of Biologicals

基　　金：国家自然科学基金资助项目(30572353)

摘　　要：目的观察小檗碱(Berberine,Ber)对实验性大鼠结肠癌的防治作用及其与过氧化物增殖物激活受体γ(Peroxi-some proliferator-activated receptorγ,PPARγ)表达的相关性。方法以二甲肼(1-2 dimethylhydrazine,DMH)40 mg/kg皮下注射加1%葡聚糖硫酸钠(Dextran sodium sulfate,DSS)水溶液饮用诱导形成大鼠结肠癌模型,以罗格列酮(Rosiglitazone,Ros)为阳性对照,观察Ber灌服对大鼠体重、异常隐窝灶(Abrrant crypt foci,ACF)和结肠癌发生率的影响。采用MTT法检测不同浓度Ber对人结肠癌lovo细胞增殖活性的影响;RT-PCR法检测Ber对lovo细胞PPARγ基因mRNA表达的情况。结果 Ber能明显改善结肠癌大鼠的恶液质状态,并阻遏体重减轻,显著减少大鼠结肠ACF数和降低结肠癌的发生率,其作用与Ros相似。Ber可呈浓度和时间依赖性抑制lovo细胞增殖,并降低lovo细胞中PPARγ基因mRNA的表达水平。结论 Ber能抑制大鼠早期ACF的形成和结肠癌发生,其作用机制可能与抑制PPARγ表达有关。Objective To observe the preventive and curative effects of berberine（Ber） on experimental colon cancer in rats and its relationship to the expression of peroxisome proliferator-activated receptor γ（PPARγ）.Methods Rat model of colon cancer was established by injection s.c.with 1-2 dimethylhydrazine（DMH） at a dosage of 40 mg / kg combined with oral administration with 1% dextran sodium sulfate（DSS） solution.The effect of oral administration with Ber on the bodyweight,abraant crypt foci（ACF） and morbidity of colon cancer of rats were observed,using rosiglitazone（Ros） as positive control.The effect of Ber at various concentrations on proliferative activity of human colon cancer lovo cells were determined by MTT method,and that on expression of PPARγ mRNA in lovo cells by RT-PCR.Results Ber improved the cachexia status and arrested the decrease of bodyweight of rats with colon cancer,while decreased the number of ACF as well as the morbidity of colon cancer in rats significantly,of which the effect was similar to that of Ros.Ber showed dosage-and time-dependent inhibitory effect on the proliferation of lovo cells,while decreased the expression level of PPARγ mRNA in lovo cells.Conclusion Ber inhibited the formation of ACF at early stage and the onset of colon cancer by a potential route which might be associated with inhibition of PPARγ expression.

关 键 词：小檗碱 结肠肿瘤 PPARΓ 

分 类 号：R735.34[医药卫生—肿瘤]