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采用小鼠悬尾试验(TST)、强迫游泳试验(FST)以及大鼠慢性温和不可预知应激(CUMS)模型评价复方柴归方超临界CO2提取物(FFCGF)的抗抑郁作用;采用核磁共振代谢组学的方法,结合多元统计分析技术探讨FFCGF的抗抑郁作用机制。大鼠进行为期28 d的CUMS程序造模,药物干预28 d,与CUMS造模同时进行,造模过程中观察大鼠体重、糖水偏爱、穿越格数和直立次数的变化,造模结束后收集大鼠尿液,应用1H-NMR技术结合多元统计分析方法分析大鼠尿液内源性代谢产物的变化规律,寻找潜在的生物标志物。结果显示FFCGF能明显减少小鼠悬尾试验和强迫游泳试验的不动时间,改善CUMS模型大鼠的体重、糖水偏爱、穿越格数和直立次数,说明FFCGF具有明确的抗抑郁作用。代谢组学结果显示空白组和模型组能明显区分,CUMS模型大鼠尿液中甘氨酸和丙酮酸含量显著升高,醋酸、琥珀酸、2-氧化戊二酸和柠檬酸含量显著降低(P<0.05,0.01),FFCGF能够明显调节CUMS程序引起的6种生物标志物的含量变化,使其恢复正常。FFCGF可能通过调节能量代谢、脂质代谢和氨基酸代谢发挥抗抑郁作用。
The antidepressant effects of Fufang Chaigui Recipe supercritical carbon dioxide extract (FFCGF) were evaluated by mouse tail suspension test (TST), forced swimming test (FST) and chronic unpredictable stress model (CUMS) in rats. Metabolomics methods, combined with multivariate statistical analysis of FFCGF antidepressant mechanism. Rats were treated with CUMS for 28 days. Drugs were administered for 28 days. Simultaneous with CUMS modeling, changes in body weight, glycogen preference, passage number and upright number were observed during modeling. Rat urine, the application of 1H-NMR technology combined with multivariate statistical analysis of urinary endogenous metabolites in rats, to find potential biomarkers. The results showed that FFCGF can significantly reduce the immobility time of mice tail suspension test and forced swimming test, and improve body weight, sugar preference, passage number and upright number of CUMS model rats, indicating that FFCGF has a definite antidepressant effect. Metabolomics results showed that the blank group and the model group can be clearly distinguished, CUMS model rat urine glycine and pyruvate content was significantly increased, acetate, succinate, 2-oxoglutarate and citric acid content was significantly reduced (P < 0.05, 0.01). FFCGF could obviously regulate the content of 6 kinds of biomarkers caused by CUMS program and make them return to normal. FFCGF may play an antidepressant effect by regulating energy metabolism, lipid metabolism and amino acid metabolism.