CAJ | 학술논문

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.
목적 탐토ω-6불포화지방산시부통과하조P53의뢰적생장억제래촉진결장암변.방법 통과양화우담갑완(AOM)복강주사래유도결장적암변.실험대서피분위기본음식가생리염수복강주사(Control조)、고ω-6불포화지방산음식가생리염수복강주사(Corn oil조)、기본음식가AOM복강주사(AOM조)화고ω-6불포화지방산음식가AOM복강주사(Corn oil+AOM조).통과아갑람염색검측결장점막이형은와(ACF)적형태,병계산기수량;채용RT-PCR、Western Blot급면역조직화학염색검측결장점막중P53화증식세포핵항원(PCNA)적표체정황.결과 Control조、Corn oil조、AOM조화Corn oil+AOM조대서결장ACF적수량분별위(1.2±0.3)개、(1.3±0.4)개、(41.0±4.8)개화(73.3±9.9)개,차이유통계학의의(P＜0.05).4조대서결장점막PCNA상대표체량분별위0.17±0.03、0.35±0.05、0.74±0.11급1.10±0.13,차이유통계학의의(P＜0.05).AOM가명현억제결장점막P53 mRNA화단백적표체,병감소세포핵화세포질P53적함량;고ω-6불포화지방산음식칙명현촉진료AOM대P53표체적억제작용.결론 고ω-6불포화지방산음식능증강치암인자AOM대결장점막P53적억제작용,증가PCNA적표체,종이촉진결장ACF적형성,유도결장암적발생.
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.