目的:研究滋阴方药二至汤对二甲基苯蒽(DMBA)诱发性乳腺癌大鼠尿液代谢物的影响。方法:60只雌性SD大鼠随机分为空白组、DMBA模型组、二至丸高、中、低剂量组(6.4,3.2,1.6 g/kg)和三苯氧胺组,除空白对照组外,每只大鼠均以致癌剂DMBA诱导(剂量100 mg/kg,2次,间隔1周)乳腺癌,诱导第2天开始给予药物干预;收集DMBA诱导后10、40、70天尿液,利用三重四级杆质谱检测其中内源性代谢物信息,利用主成分分析,正交信号校正偏最小二乘法判别分析动物尿液代谢物组学特征及生物标记物。结果:与空白组比较,DMBA诱导40天时对大鼠尿液代谢物影响最为显著,内源性代谢物中共有36个生物标记物发生变化;二至汤6.4g/kg对20个生物标记物有明显干预作用,其中胆碱、邻吡啶甲酸、肌肽、异丁酰-左旋-肉毒碱及皮质醇的含量和模型组相比有所回调。结论:二至汤可以调节DMBA诱发性乳腺癌大鼠体内的代谢物紊乱,为研究二至汤抑制乳腺癌发生发展的有效性与合理性提供了依据。
To study the effect of Erzhi decoction in breast cancer induced by 7, 12-dimethylbenz(a) anthrancene(DMBA) in rats. Methods: The 60 female SD rats were randomly divided into 6 groups : the blank control group, the DMBA model group, the high, middle, low dose (6.4,3.2,1.6 g/kg) Erzhi group and tamoxifen(TAM) group. All rats were induced by DMBA (100mg/kg, twice, with one week interval), except the blank control group. The urine of rats were collected after induction at 10, 40, 70 days and analyzed by LC-MS/MS. The acquired data were analyzed by OSC-PLS-DA. Results: After administration for 40 days, endogenous metabo]Jtes concentration in the u- fine of administrated rats changed apparently. Through OSC-PLS-DA analysis, compared with the control group 36 biomarkers were found in the DMBA model group, and which given high Erzhi decoction caused certain 20 endogenous substances to reverse changes, especially cho- line,pyridine-2-carboxylic,carnoslne, Isobutyryl-L-camitine, and cortisol. Conclusion: The administration of Erzhi decoction could have changed endogenous metabolites concentration, it provides the validity and reasonableness for Erzhi decoction to inhibit the growth of breast tumor.