基于肝脏代谢组学的当归“活血解郁”作用机制研究

目的 研究当归Angelicae Sinensis Radix“解郁”功效与“活血”功效的相关性及机制。方法 采用慢性不可预见性温和应激（chronic unpredicted mild stress，CUMS）结合孤养复制大鼠抑郁模型，以行为学指标及血流变指标评价当归对CUMS大鼠抑郁样症状及血液黏度的调节作用，进行主成分分析和相关性分析量化抗抑郁指标和血流变指标间的相关性。应用¹H-NMR代谢组学技术检测CUMS大鼠肝脏中内源性代谢物的变化，指认相关差异代谢物并构建代谢通路。结果 造模4周后，大鼠体质量、糖水偏爱率、旷场实验穿越格数、直立次数均显著降低（P<0.01），高、中、低切变率下的全血黏度均显著升高（P<0.01）。给予当归干预后，大鼠的行为学指标和血流变指标均有不同程度的改善。相关性分析结果显示，行为学综合指标与血流变综合指标呈显著负相关。代谢组学结果显示，在筛选得到的19个潜在生物标志物中，当归能显著回调异亮氨酸、缬氨酸、乳酸、丙氨酸、柠檬酸等8种差异代谢物，涉及缬氨酸、亮氨酸和异亮氨酸合成，乙醛酸和二羧酸代谢及甘油脂代谢等5条代谢通路。结论 当归的“解郁”功效与其“活血”功效存在显著相关性，其机制可能与调节氨基酸代谢、碳水化合物代谢、脂质代谢等代谢途径有关。

Mechanism of Angelicae Sinensis Radix on anti-depression and activating blood based on liver metabolomics

Objective To study the correlation and mechanism between the efficacy of anti-depression and activating blood of Danggui (Angelicae Sinensis Radix). Methods The depression model of rats was established through chronic unpredictable mild stress (CUMS) procedure combined with solitary. The behavioral indexes and hemorheology indexes were used to evaluate the effect of Angelicae Sinensis Radix on depression-like symptoms and blood viscosity of CUMS rats. Principal component analysis and correlation analysis were carried out to evaluate the correlation between the behavioral indexes and hemorheology indexes. The changes in endogenous metabolites and metabolic pathways in liver of CUMS rats were detected by proton nuclear magnetic resonance spectroscopy (¹H-NMR). Results After modeling for four weeks, body weight, sucrose preference rate, crossing grid number and standing times in open field test of rats were significantly decreased (P < 0.01), while the whole blood viscosity at low-, middle-, and high-shear rates were significantly increased (P < 0.01). After the intervention of Angelicae Sinensis Radix, the behavioral indexes and hemorheology indexes of rats had improvement in different degree. The results of correlation analysis showed that the comprehensive index of behavior was significantly negatively correlated with the comprehensive index of hemorheology. Metabolomics analysis showed that among the 19 potential biomarkers screened, Angelicae Sinensis Radix could significantly call back eight differential metabolites such as isoleucine, valine, lactic acid, alanine, citric acid, etc. The metabolites were involved in five metabolic pathways including valine, leucine and isoleucine synthesis, glyoxylic acid and dicarboxylic acid metabolism, glycerolipid metabolism, etc. Conclusion There is a significant correlation between the effect of anti-depression and activating blood of Angelicae Sinensis Radix. The mechanism may be related to the regulation of amino acid metabolism, carbohydrate metabolism and lipid metabolism.