【作者】 张典； 弥曼； 姜凤良； 孙阳； 李宇华； 樊磊； 梅其炳；

【Author】 ZHANG Dian 1,2 ,MI Man 1 ,JIANG Feng-liang 1 , SUN Yang 2 ,LI Yu-hua 2 ,FAN Lei 2 and MEI Qi-bing 2( 1 Department of Pathogen Biology and Immunology, Xi’an Medical University. Xian 710021,China; 2 Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xian 710032, China)

【机构】 西安医学院病原生物学与免疫学教研室； 第四军医大学药理学教研室；

【摘要】 目的:研究苹果多糖对结肠炎癌变的预防作用,并探讨其作用机制。方法:使用致炎剂DSS和致癌剂AOM,建立小鼠结肠炎相关结直肠癌动物模型。从苹果渣中提取苹果多糖,通过免疫组织化学、Westernblot、ELISA等方法观察苹果多糖预防用药对各组小鼠血清中促炎细胞因子TNF-α以及组织中TLR4、MyD88、NF-κBp65蛋白的影响。结果:病理检测结果发现,与模型组(95%致癌率)相比,苹果多糖将结直肠肿瘤的发生率降至26%,10%,and5%inAP(1.25,2.5,and5%),且呈剂量依赖性。与模型组相比,免疫组化结果发现,苹果多糖各个剂量组均降低结直肠组织中TLR4表达;westernblot结果显示:苹果多糖各个剂量组均降低结直肠组织中TLR4、MyD88和NF-κBp65蛋白表达;ELISA结果显示,苹果多糖各剂量组小鼠血清中TNF-α水平明显降低(P<0.05)。结论体内实验表明,苹果多糖可有效预防结肠炎癌变,其作用机制可能与其抑制TLR4/MyD88/NF-κB通路有关。更多还原

【Abstract】 OBJECTIVE To study the effects and mechanisms of apple polysaccharides on tumorigenesis in a mouse model of colitis-associated colon cancer. METHODS we obtained apple polysaccharides from apple pomace and evaluated its protective efficacy on carcinogenesis in a mouse model of colitis-associated colon cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). The effect of AP on TLR4/MyD88/NF-κB pathway were measured using immunohistochemistry and Western blot.The serum were collected and TNF-α was measured by ELISA kits. RESULT After 20 weeks of continuous treatment,the incidence of colon cancer formation was 95% in the mice treated with AOM/DSS (model group), and these reduced to 26%, 10%, and 5% in AP (1.25, 2.5, and 5%) treatment group respectively. Western blot analysis demonstrated that TLR4 (membrane protein), MyD88, NF-κB p65 (nuclear protein) expression increased significantly at protein level and NF-κB pathway was significantly activated in model group; the secretion of TNF-α increased in model group. AP treatment significantly decreased the elevation of all the biomarkers mentioned above induced by AOM/DSS. CONCLUSIONS AP could protect ICR mice from CACC effectively and the possible mechanism may be related to the inhibition of TLR4/MyD88/ NF- B pathways.更多还原