ω-6不饱和脂肪酸促进结肠癌变的实验研究  

Omega-6 polyunsaturated fatty acid promotes colon carcinogenesis

作　　者：陈小良[1] 李建忠[1] 曾利娴[1] 詹雅诗[1] 杨英慧[1] 杨齐[1] 刘慧玲[1] 吴斌[1] 

机构地区：[1]中山大学附属第三医院消化科,广州510630

出　　处：《中华胃肠外科杂志》2010年第10期774-777,共4页Chinese Journal of Gastrointestinal Surgery

基　　金：基金项目：国家自然科~（30971357）;广东省科技计划项目（20098060300001）

摘　　要：目的 探讨ω-6不饱和脂肪酸是否通过下调P53依赖的生长抑制来促进结肠癌变.方法 通过氧化偶氮甲烷（AOM）腹腔注射来诱导结肠的癌变.实验大鼠被分为基本饮食加生理盐水腹腔注射（Control组）、高ω-6不饱和脂肪酸饮食加生理盐水腹腔注射（Corn oil组）、基本饮食加AOM腹腔注射（AOM组）和高ω-6不饱和脂肪酸饮食加AOM腹腔注射（Corn oil＋AOM组）.通过亚甲蓝染色检测结肠黏膜异型隐窝（ACF）的形态,并计算其数量 采用RT-PCR、Western Blot及免疫组织化学染色检测结肠黏膜中P53和增殖细胞核抗原（PCNA）的表达情况.结果 Control组、Corn oil组、AOM组和Corn oil＋AOM组大鼠结肠ACF的数量分别为（1.2±0.3）个、（1.3±0.4）个、（41.0±4.8）个和（73.3±9.9）个,差异有统计学意义（P＜0.05）.4组大鼠结肠黏膜PCNA相对表达量分别为0.17±0.03、0.35±0.05、0.74±0.11及1.10±0.13,差异有统计学意义（P＜0.05）.AOM可明显抑制结肠黏膜P53 mRNA和蛋白的表达,并减少细胞核和细胞质P53的含量 高ω-6不饱和脂肪酸饮食则明显促进了AOM对P53表达的抑制作用.结论 高ω-6不饱和脂肪酸饮食能增强致癌因子AOM对结肠黏膜P53的抑制作用,增加PCNA的表达,从而促进结肠ACF的形成,诱导结肠癌的发生.Objective To investigate whether ω-6 polyunsaturated fatty acid promotes colon carcinogenesis through downregulation of P53-dependent growth inhibition. Methods Colon carcinogenesis was induced by injection of azoxymethane（AOM） intraperitoneally. Experimental animals were randomly divided into four groups, receiving regular diet and intraperitoneal injection of normal saline（control group）, high ω-6 polyunsaturated fatty acid diet with intraperitoneal injection of normal saline（Corn oil group）, regular diet with intraperitoneal injection of AOM（AOM group）, or high ω-6 polyunsaturated fatty acid diet with intraperitoneal injection of AOM （Corn oil＋AOM group）. Aberrant crypt focis （ACFs） were observed after methylene blue staining and enumerated. Colonic mucosa PCNA and P53 expressions were assessed by RT-PCR and Western blotting, and location of P53 in the colon crypt focis was determined by immunohistochemical staining. Results Amounts of ACFs was 1.2±0.3 in the control group, 1.3±0.4 in the Corn oil group, 41.0±4.8 in the AOM group, and 73.3±9.9 in the Corn oil＋AOM group, the differences were statistically significant（P〈0.05）. The expression of P53 in normal crypt focis was higher than that in ACFs. High ω-6 polyunsaturated fatty acid dietary significantly promoted AOM-induced colon PCNA expression, and enhanced AOM-mediated P53 inhibition in colon mucosa. Conclusion High ω-6 polyunsaturated fatty acid diet can enhance AOM-induced inhibition of P53 in colon mucosa, resulting in overexpression of PCNA, formation of ACF, and carcinogenesis in the colon.

关 键 词：结肠肿瘤 ω-6不饱和脂肪酸 基因 P53 增殖细胞核抗原 

分 类 号：R735[医药卫生—肿瘤]