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目的基于核磁共振法对小鼠乳腺癌血清代谢组学的研究,揭示绿原酸抗肿瘤相关生物标记物和抗癌作用靶点。方法以小鼠(Balb-c/EMT-6)乳腺癌为疾病模型,设立绿原酸治疗组(CHA,20mg/kg,qd)、多西他赛(DX,5mg/kg,qod)治疗阳性对照组、肿瘤模型组、空白组;小鼠血清去蛋白后,测定并采集各样品的核磁共振(NMR)谱,对比不同周期各组血清波谱特征的差异;采用PLS-DA模式识别分析,计算出各组波谱参数的统计学关系。结果各个特征峰的归属分别为乳酸(δ1.32-1.36ppm)、丙氨酸(δ1.48ppm)、乙酸(δ1.92ppm)、缬氨酸(δ2.26ppm)、丙酮酸(δ2.38ppm)、柠檬酸(δ2.5~2.75ppm)、肌酸(δ3.05ppm)、胆碱(δ3.20~3.22ppm)、葡萄糖(δ3.75ppm);PLS-DA模式识别分析使各组参数得到有效区分;CHA组和DX组出现部分重叠,接近于空白组并区别于模型组,随着治疗周期的延长,这些现象呈现加强的趋势。经绿原酸治疗后,血清中胆碱、肌酸和柠檬酸等代谢组分与模型组相关代谢组分比较呈减小趋势(P>0.1),乳酸、丙氨酸、乙酸、和丙酮酸呈现较明显下降趋势(P≤0.1);随着治疗的深入,上述关联代谢组分的变化趋势随着抑瘤率的逐渐增加而得到加强。结论小鼠乳腺癌血清中乳酸、丙氨酸、乙酸、肌酸、柠檬酸、胆碱、丙酮酸等代谢物的变化水平与肿瘤的生长密切相关,意味着经过深入验证后可成为表达肿瘤生长状态的生物标记物。根据乳酸、丙氨酸、乙酸、肌酸、柠檬酸、胆碱、丙酮酸等无氧糖酵解代谢物的变化,推测绿原酸可能通过抑制肿瘤能量代谢途径发挥抗癌作用。
Objective To study the serum metabonomics of mouse mammary cancer based on NMR and to reveal the anti-tumor biomarkers and anti-cancer targets of chlorogenic acid. Methods Mouse (Balb-c/EMT-6) breast cancer was used as a disease model to establish chlorogenic acid treatment group (CHA, 20 mg/kg, qd) and docetaxel (DX, 5 mg/kg, qod) treatment positive Control group, tumor model group and blank group; after deproteinized mice serum, the nuclear magnetic resonance (NMR) spectra of each sample were measured and collected to compare the difference of serum spectrum characteristics of each group at different periods; PLS-DA pattern recognition analysis was used to calculate The statistical relationship between the spectral parameters of each group. As a result, the respective characteristic peaks were attributed to lactic acid (δ1.32-1.36 ppm), alanine (δ 1.48 ppm), acetic acid (δ 1.92 ppm), valine (δ 2.26 ppm), and pyruvic acid (δ 2.38 ppm). , Citric acid (δ2.5~2.75ppm), Creatine (δ3.05ppm), Choline (δ3.20~3.22ppm), Glucose (δ3.75ppm); PLS-DA pattern recognition analysis enabled each group of parameters to be valid Differentiation; CHA group and DX group appear partial overlap, close to the blank group and different from the model group, with the extension of the treatment cycle, these phenomena show a trend of strengthening. After chlorogenic acid treatment, serum choline, creatine and citric acid and other metabolic components showed a trend of decrease (P>0.1) compared with the model group-related metabolic components. Lactic acid, alanine, acetic acid, and pyruvate There was a significant downward trend (P ≤ 0.1); as the treatment progressed, the trend of the above-mentioned associated metabolic components was strengthened with the gradual increase in tumor inhibition rate. CONCLUSIONS: The levels of metabolites such as lactic acid, alanine, acetic acid, creatine, citric acid, choline, and pyruvate in the serum of mouse breast cancer are closely related to the growth of tumors, which means that they can become tumor growth after thorough verification. State biomarkers. Based on the changes in anaerobic glycolytic metabolites such as lactic acid, alanine, acetic acid, creatine, citric acid, choline, and pyruvate, it has been speculated that chlorogenic acid may play an anti-cancer role by inhibiting tumor energy metabolism pathways.