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异甘草素对氧化偶氮甲烷和右旋葡聚糖苷钠诱导小鼠炎症相关结肠癌的预防作用及其机制 被引量:2

Preventive effect and mechanism of different doses of isoliquiritigenin on the induction of inflammation related colon cancer in mice induced by azoxymethane and dextran sodium sulfate
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摘要 目的探讨异甘草素(isoliquiritigenin,ISL)对结肠炎相关结肠癌的预防作用及其机制。方法 50只雄性BALB/c小鼠随机分为5组,每组10只:正常对照组;模型对照组;低、中、高剂量组。每天观察小鼠一般情况,每周测体质量1次,12周后处死小鼠,观察结肠癌发生率及结肠长度的变化,美蓝染色法观察异常隐窝灶(aberrant crypt foci,ACF)数量,病理形态学观察小鼠结肠组织形态学改变,免疫组化法检测组织中巨噬细胞甘露糖受体(CD206)、环氧合酶(COX)-2和一氧化氮合酶(i NOS)的表达水平。结果模型对照组小鼠在实验过程中均出现消瘦、厌食、脱毛、血便等表现。三个剂量给药组一般情况均明显优于模型对照组。在实验第12周,模型对照组小鼠体质量显著低于正常对照组,而中、高剂量给药组小鼠体质量显著高于模型对照组;模型对照组小鼠结肠长度显著低于正常对照组,而中、高剂量给药组小鼠结肠长度较模型对照组显著增加。三个剂量给药组与模型对照组比,肿瘤发生率呈浓度依赖性减少;三个剂量给药组ACF数量与模型对照组比较显著降低;与模型对照组相比,三个剂量给药组随着ISL浓度的增加,肠黏膜愈来愈完整,隐窝形态逐渐恢复,炎性细胞浸润愈来愈少;三个剂量给药组CD206、COX-2和i NOS表达水平与模型对照组相比,呈剂量依赖性降低。结论 ISL对AOM/DSS诱导的小鼠结肠炎相关结肠癌发生具有明显预防作用,其作用机制可能与其能抑制巨噬细胞向M2型转化及下调COX-2和i NOS表达有关。 Objective To investigate the effect of isoliquiritigenin (ISL) on the prevention of colitis associated colon cancer. Methods Fifty male BALB/c mice were randomly divided into 5 groups, each group was 10 mice: normal control group, model group, ISL low dose group, ISL middle dose group, ISL high dose group. Mice were observed for weight and other general condition, incidence of colon cancer and colon length changes; methylene blue staining was used to observe number of aberrant crypt loci (ACF) ; pathological morphology was used to observe morphological changes; immunohistochemistry method was used to detect macrophage mannose receptor (CD206), cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expressions in colon tissue. Results The model group appeared emacia- tion, anorexia, hair removal, stool performance during the experiment. The three doses of ISL groups were significantly better than the model cont group. At the twelfth week, the weight of mice in model group was significantly lower than that in normal control group, while the mice in high dose group and middle dose group were significantly higher than that in model group, and the length of colon in model group was significantly lower than that in normal control group. Com- pared with model group, the incidence of tumor was significantly lower than that in 3 ISL dose groups, and the number of ACF in model group was significantly lower than that in 3 ISL dose groups, and the number of iNOS, COX-2 and CD206 expressions in three dose groups were decreased significantly. Conclusion ISL has cbemoprevention on AOM/ DSS-induced mouse colon cancer. ISL can inhibit macrophages in the tumor mieroenvironment convert to M2 type and reduce COX-2 and iNOS expressions in colon tissue.
作者 冯言晓
出处 《胃肠病学和肝病学杂志》 CAS 2017年第8期873-878,共6页 Chinese Journal of Gastroenterology and Hepatology
关键词 异甘草素 结肠炎相关结肠癌 肿瘤相关巨噬细胞 CD206 Isoliquiritigenin Colitis-associated colon cancer Tumor associated macrophage CD206
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