代谢组学研究复方柴归方超临界CO_2提取物抗抑郁作用及其机制

Anti-depressant effect and mechanism of supercritical CO_2 extract from Compound Chaigui Fang

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 tail suspension test（ TST）,forced swimming test（ FST） and chronic unpredictable mild stress（ CUMS） model were used to evaluate the anti-depressant effect of supercritical CO2extract from Compound Chaigui Fang（ FFCGF）. A nuclear magnetic resonance（ NMR）-based metabonomics combined with multivariate statistical analysis was performed to explore the mechanism of FFCGF. Rats were conducted by CUMS procedure for 28 days and drugs were administrated at the same time. The body weight,sucrose preference,crossings and rearings in open-field tests were evaluated and the urine was collected simultaneously. The metabonomic profiles of rats＇ urine were analyzed by NMR and potential biomarkers were searched by multivariate statistical analysis. The results showed that administration of FFCGF significantly decreasing the immobility time in FST and TST and improving rats＇ body weight,sucrose preference,crossings and rearings in CUMS,which were indication that the anti-depressant effect of FFCGF was abvious. Significant differences in the metabolic profile of the CUMS treated group and the control group were observed,which were consistent with the results of behavioral tests. Decreased levels of acetic acid,succinic acid,2-oxidation glutaric acid and citric acid and increased glycine and pyruvic acid in urine were significantly affected by the CUMS procedure and the 6 biomarkers were reversed evidently after administration of FFCGF. These changes were suggestion that the anti-depressant mechanism of FFCGF was associated with energy metabolism,lipid metabolism and amino acid metabolism.