n-3 PUFAs对MNU诱发大鼠结直肠癌形成的影响及机制

Influence of n-3 PUFAs on colorectal tumor formation induced by MNU in rats and the mechanism

目的:探讨n-3多不饱和脂肪酸(n-3 PUFAs)对N-甲基-N-亚硝基脲(MNU)诱发大鼠结直肠癌模形成的影响及机制。方法:将60只SD大鼠随机均分为实验组和对照组。两组均用MNU进行灌肠诱导结直肠癌,实验组同时行n-3 PUFAs灌胃,而对照组以等量生理盐水灌胃。16周后,比较两组大鼠的一般情况;处死大鼠,观察肿瘤发生情况及肿瘤病理特征,气相色谱测定红细胞膜n-3 PUFAs浓度,液相色谱串联质谱检测外周血细胞总DNA甲基化水平。结果:实验组大鼠便血发生率低于对照组、进食量及体质量大于对照组(均P<0.05)。两组大鼠均有结直肠肿瘤形成,肿瘤均为腺癌,但与对照组比较,实验组结直肠肿瘤形成率明显降低(63.33%vs.86.67%,P<0.05),且肿瘤最大径小、多发肿瘤少。实验组大鼠红细胞膜n-3 PUFAs浓度、外周血细胞总DNA甲基化水平明显高于对照组(均P<0.05)。结论:n-3 PUFAs能有效抑制MNU诱导的大鼠结直肠癌发生,可能与其提高DNA甲基化水平有关。

Objective：To investigate the influence of n-3 polyunsaturated fatty acids（n-3 PUFAs） on colorectal tumor formation induced by N-methyl-N-nitrosourea（MNU） in rats and the mechanism.Methods：Sixty SD rats were equally randomized into experimental group and control group.Rats in both groups underwent administration of MNU by enema to induce colorectal cancer,and simultaneously,those in experimental group were gavaged with n-3 PUFAs,while those in control group were administered the same volume of saline in the same fashion.Sixteen weeks later,the general conditions between the two groups of rats were compared,at er that,rats were sacrii ced,the tumor occurrence and pathological features of the tumors wereobserved,the concentration of n-3 PUFAs in erythrocyte membrane was measured by gas chromatography,and global methylation level in peripheral blood cells was determined by liquid chromatography-mass spectrometry.Results：The incidence of hematochezia was lower,and food-intake as well as body weight gain were greater in experimental group than those in control group（all P〈0.05）.Colorectal tumor formation was found in both group of rats and all tumors were identii ed as adenocarcinoma,but the tumor formation rate in experimental group was signii cantly lower than that in control group（63.33% vs.86.67%,P〈0.05）,with reduced tumor size and multiple lesions.The concentration of n-3 PUFAs in erythrocyte membrane and global methylation level in peripheral blood cells in experimental group were signii cantly higher than those in control group（both P〈0.05）.Conclusion：n-3 PUFAs can effectively inhibit the occurrence of colorectal cancer induced by MNU in rats,which may probably be associated with their promotion of DNA methylation.