基于代谢组学技术的田黄方配伍机制分析

Analysis of Compatibility Mechanism of Tianhuang Fang Based on Metabonomics

【目的】观察田黄方不同组方对血脂及代谢产物的影响,揭示其治疗高脂血症的组方机制。【方法】取雄性SD大鼠30只,分为正常组、模型组、三七组、黄连组及田黄组。采用高脂乳剂灌胃法复制高脂血症大鼠模型并给予相应药物治疗,采集治疗4周后的血液,采用超高效液相色谱串联四级杆飞行时间质谱联用(UPLC/Q-TOF MS)技术建立大鼠血清的代谢物指纹图谱。应用主成分分析和偏最小二乘判别分析模型组和田黄组、三七组、黄连组之间的代谢物谱差异,并通过变量重要性投影(VIP)选取生物标志物,比较各组的标志物并找出差异。【结果】田黄方对饮食性高脂血症大鼠模型的干预作用主要体现在对脂肪代谢、氨基酸代谢、炎症和氧化应激的调节作用,而三七、黄连虽能一定程度改善模型组大鼠的代谢紊乱状态,但未能从根本上恢复。【结论】田黄方对高脂血症动物模型血脂及代谢产物的调节作用优于三七、黄连单用,其中三七以调节氨基酸代谢、能量代谢为主,黄连以调节炎症、氧化应激及能量代谢为主,田黄方对上述代谢紊乱均有调节作用。

Objective To study the effects of Tianhuang Fang, a prescription composed of Radix Notoginseng （Sanqi） and Rhizoma Coptidis （Huanglian）, and its separated prescriptions on blood lipids and metabolic products , and to explore the compatibility rule of Tianhuang Fang in treating hyperlipidemia. Methods Thirty male SD rats were randomly divided into 5 groups, namely normal group, model group, Sanqi group, Huanglian group, and Tianhuang Fang group. Rat model of hyperlipidemia was established by intragastric administration of high-fat emulsion, and then the modeled rats were given corresponding medication respectively. After treatment for 4 weeks, serum samples were collected for the establishment of metabolism fingerprint by ultra-performance liquid chromatography / quadrupole time-of-flight mass spectrometry（UPLC/Q- TOF MS）. The differences of metabolism fingerprint in the above groups were studied by principal component analysis （PCA）and partial least squares-discriminant analysis （PLS-DA）, and then biomarkers were screened by variable importance in the projection （VIP）and compared in various groups. Results Tianhuang Fang had an effect on regulating the fat metabolism, amino acid metabolism, inflammation, andoxidative stress of diet- induced hyperlipidemia rats, while Tianqi and Huanglian only improved some aspects of metabolic disorders to a certain degree. Conclusion Tianhuang Fang has better effect on the regulation of blood lipids and metabolites than Sanqi and Huanglian. Sanqi mainly regulates amino acid and energy metabolism, Huanglian plays a role in regulating inflammation, oxidative stress and energy metabolism, while Tianhuang Fang has an overall effect on the above metabolic disorders.