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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 effect and mechanism of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the formation of colorectal cancer in rats induced by N-methyl-N-nitrosourea (MNU). Methods: 60 SD rats were randomly divided into experimental group and control group. Both groups were enema with MNU to induce colorectal cancer, while experimental group n-3 PUFAs gavage, while the control group with the same amount of normal saline. After 16 weeks, the general conditions of the two groups were compared; the rats were killed to observe the tumor occurrence and tumor pathological features; the concentration of erythrocyte n-3 PUFAs was determined by gas chromatography; the total DNA methylation of peripheral blood was detected by liquid chromatography-tandem mass spectrometry Level. Results: The incidence of hematochezia in the experimental group was lower than that in the control group, and the food intake and body weight were higher than those in the control group (all P <0.05). The colorectal tumor was formed in both groups and the tumors were all adenocarcinoma. However, compared with the control group, the colorectal tumor formation rate in the experimental group was significantly decreased (63.33% vs.86.67%, P <0.05), and the largest diameter , Multiple tumor less. The concentration of n-3 PUFAs in erythrocyte membrane and total DNA methylation in peripheral blood of rats in experimental group were significantly higher than those in control group (all P <0.05). CONCLUSION: n-3 PUFAs can effectively inhibit MNU-induced colorectal cancer in rats, which may be related to the increase of DNA methylation level.