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目的探讨核受体基因表达在不同膳食脂肪酸影响大鼠乳腺癌发生中的作用。方法用8种不同膳食脂肪酸(饱和脂肪酸、单不饱和脂肪酸、n-6多不饱和脂肪酸、n-3多不饱和脂肪酸、1:1 n-6/n-3多不饱和脂肪酸、5:1 n-6/n-3多不饱和脂肪酸、10:1 n-6/n-3多不饱和脂肪酸、1:2:1饱和脂肪酸/单不饱和脂肪酸/多不饱和脂肪酸其中 n-6/n-3多不饱和脂肪酸1:1)喂养 SD 雌性幼年大鼠,采用50 mg/kg 的甲基亚硝基脲单次腹腔注射诱导大鼠乳腺癌发生,电镜观察大鼠乳腺细胞结构变化,BrdU 体内标记法检测大鼠乳腺细胞增殖活性,RT-PCR 分析乳腺组织过氧化物酶增殖活化受体(PPARB 和 PPARγ)mRNA 表达。结果无乳腺癌诱发的各对照和 n-3多不饱和脂肪酸诱癌组大鼠乳腺细胞超微结构正常,细胞增殖活性低。而有大鼠乳腺癌诱发的组织细胞内可见明显的腺癌标志,且高乳腺癌诱发的饱和脂肪酸、单不饱和脂肪酸、n-6多不饱和脂肪酸、5:1 n-6/n-3多不饱和脂肪酸、10:1 n-6/n-3多不饱和脂肪酸和1:2:1饱和脂肪酸/单不饱和脂肪酸/多不饱和脂肪酸喂养组大鼠乳腺细胞增殖活性升高(BrdU 阳性率为21%～22%),但1:1 n-6/n-3多不饱和脂肪酸低诱癌组乳腺细胞增殖活性明显降低上述高乳腺癌诱发组(BrdU 阳性率为13%,P<0.05)。此外,过氧化物酶增殖活化受体作为与脂代谢密切相关的细胞核受体基因,1:1 n-6/n-3多不饱和脂肪酸低诱癌组较相应对照组上调 PPARβ和 PPARγmRNA 表达力度明显弱于高乳腺癌诱发组。结论不同膳食脂肪酸对 PPAR 基因表达的调节截然不同,这可能是差异性调节大鼠乳腺癌发生的分子机制之一。
Objective To investigate the role of nuclear receptor gene expression in the development of breast cancer in rats with different dietary fatty acids. Methods Eight different dietary fatty acids (saturated fatty acids, monounsaturated fatty acids, n-6 polyunsaturated fatty acids, n-3 polyunsaturated fatty acids, 1: 1 n-6 / n-3 polyunsaturated fatty acids, n-6 / n-3 polyunsaturated fatty acids, 10: 1 n-6 / n-3 polyunsaturated fatty acids, 1: 2: 1 saturated fatty acids / monounsaturated fatty acids / polyunsaturated fatty acids where n-6 / n -3 polyunsaturated fatty acids 1: 1) were fed to SD female young rats. The rats were induced by single intraperitoneal injection of methyl nitrosourea (50 mg / kg), the ultrastructural changes of breast cells were observed by electron microscope, BrdU The proliferation of rat mammary cells was detected by in vivo labeling method. The mRNA expression of peroxisome proliferator activated receptor (PPARB and PPARγ) in breast tissues was analyzed by RT-PCR. Results No breast cancer induced in each control and n-3 polyunsaturated fatty acid induced cancer rats normal ultrastructure of breast cells, low cell proliferation. The breast cancer-induced tissue cells showed obvious signs of adenocarcinoma, and high breast cancer-induced saturated fatty acids, monounsaturated fatty acids, n-6 polyunsaturated fatty acids, 5: 1 n-6 / n-3 Increased proliferative activity of breast cells in polyunsaturated fatty acids, 10: 1 n-6 / n-3 polyunsaturated fatty acids and 1: 2: 1 saturated fatty acids / monounsaturated fatty acids / polyunsaturated fatty acids fed groups (BrdU positive (21% -22%). However, the proliferation activity of breast cancer cells in low induction group of 1: 1 n-6 / n-3 polyunsaturated fatty acids was significantly lower than that of the high breast cancer induction group (BrdU positive rate was 13%, P < 0.05). In addition, peroxisome proliferator-activated receptor, a nuclear receptor gene closely related to lipid metabolism, upregulated the expression of PPAR|Â and PPAR|ÃmRNA in low-induction group of 1: 1 n-6 / n-3 polyunsaturated fatty acids Obviously weaker than the high breast cancer induced group. Conclusion Different dietary fatty acids regulate the expression of PPAR gene differently, which may be one of the molecular mechanisms that differentially regulate the occurrence of breast cancer in rats.