重楼皂苷Ⅵ预防结肠炎癌变的作用及机制  

Polyphyllin Ⅵ inhibits colitis associated colorectal carcinogenesis in mice: Possible mechanisms

作　　者：李志泉[1] 陈晓艳[1] 岳正刚[2] 周慧萍[1] 陈永春[1] 熊春四[1] 郑洪南 李宇华[1] 

机构地区：[1]中国人民解放军第422医院药剂科,广东省湛江市524005 [2]中国人民解放军第四军医大学药学系药理教研室,陕西省西安市710032

出　　处：《世界华人消化杂志》2014年第29期4393-4398,共6页World Chinese Journal of Digestology

摘　　要：目的:讨论从延龄草总皂苷中分离获得的重楼皂苷Ⅵ(polyphyllinⅥ,PPLⅥ)对结肠炎相关的结肠癌发生的影响及其机制.方法:将♂5周龄ICR小鼠50只,随机分为5组:模型组、3个给药组和对照组.模型组与给药组小鼠腹腔注射15 mg/kg的1,2-二甲肼(1,2-dimethylhydrazine,DMH).1 wk后,饮用2%右旋葡聚糖苷钠(dextran sodium sulfate,DSS)蒸馏水溶液1 wk,间隔1 wk后,再次饮用2%DSS蒸馏水溶液1 wk.第9周时,给药组小鼠通过腹腔注射给予PPLⅥ(2.5、5.0、10.0mg/kg),1次/3 d.20 wk乙醚麻醉,处死所有小鼠,收集小鼠肠道样本,用于病理学检测及Western blot实验.结果:HE染色显示:模型组中,90%的小鼠肠道发生结肠腺癌和/或结肠腺瘤.PPLⅥ治疗各组,小鼠结/直肠肿瘤发生率依次下降为:40%、20%与10%.PPLⅥ可促进小鼠肠道黏膜活化型Caspase3,9及Bax的表达,降低Bc1-2的表达,且均呈剂量依赖性.结论:PPLⅥ能有效地预防小鼠结肠炎癌变.其可能机制是PPLⅥ通过线粒体途径诱导小鼠肠道细胞凋亡.AIM： To investigate the effect of polyphyllin Ⅵ（PPLⅥ） on colitis associated colorectal carcinogenesis in mice and the underlying mechanisms. METHODS： Fifty male Institute of Cancer Research（ICR） mice were randomly divided into five groups： a model group, three PPLⅥ-treated groups and a control group. The mice in the model group and three PPLⅥ-treated groups were given a single intraperitoneal injection of 1,2-dimethylhydrazine（DMH） at a dose of 15 mg/kg body weight. One week later, the mice were treated with 2%（w/v） dextran sodium sulfate（DSS） in theirdrinking water for 1 wk. This was followed by no further treatment for 1 wk. After another 1 wk of 2% DSS treatment, normal water was given for an additional 15 weeks. At week 9, the mice in PPLⅥ-treated groups were intraperitoneally injected with PPLⅥ（2.5, 5.0 and 10.0 mg/kg, respectively） every 3 d, for 12 wk. All mice were sacrificed at week 20 by ether overdose and colon samples were collected for histopathological examinations and Western blot analysis.RESULTS： HE staining showed that the incidence of tumor formation was 90% in the mice treated with DMH/DSS; it decreased to 40%（4/10）, 20%（2/10）, and 10%（1/10） in mice treated with DMH/DSS plus 2.5, 5.0 and 10.0 mg/kg of PPLⅥ, respectively. PPLⅥ treatment increased the expression of cleaved Caspase3, Caspase9 and Bax and decreased the expression of Bcl-2 in colonic epithelial cells. CONCLUSION： PPLⅥ can inhibit DMH/DSS-induced colon tumor formation in ICR mice partly through inducing apoptosis of abnormal colonic epithelial cells via the intrinsic pathway of apoptosis.

关 键 词：重楼皂苷Ⅵ 结肠癌 凋亡 

分 类 号：R735.34[医药卫生—肿瘤]