[关键词]
[摘要]
目的比较不同品种柴胡(南柴胡和北柴胡)组成的逍遥散的抗抑郁功效,探寻其对大鼠内源性代谢产物变化规律的影响。方法采用慢性温和不可预知应激程序对大鼠进行为期4周的抑郁造模,在造模2周后分别ig给予由南柴胡或北柴胡组成的逍遥散(生药)46 g/kg水提取液、文拉法辛0.05 g/kg干预,每天1次,连续给药2周,观测动物行为学症状。应用核磁共振(1H-NMR)方法分析大鼠血清内源性代谢产物的变化规律。结果 2种逍遥散和文拉法辛对抑郁大鼠行为学指标均有显著影响,与模型组比较差异显著(P<;0.05、0.01)。代谢组学研究结果显示,2种逍遥散和文拉法辛干预后,大鼠血清中异亮氨酸、氧化三甲胺、胆碱水平升高,而乳酸、N-乙酰糖蛋白、肌酸、苏氨酸及β-葡萄糖等水平降低,与模型组比较差异显著(P<;0.05、0.01)。2个逍遥散组对抑郁大鼠行为学指标的影响组间比较未显示统计学差异。结论不同品种柴胡组成的逍遥散均具有明显的抗抑郁作用,但功效有所差别,即南柴胡组成逍遥散的抗抑郁效果及起效时间略优于北柴胡。应用行为学与代谢组学相结合的方法评价逍遥散抗抑郁功效具有准确性好、灵敏度高等特点。
[Key word]
[Abstract]
ObjectiveTo compare the antidepressive effects of Xiaoyao Powder (XYP) composed of Bupleurum scorzonerifolium(Nan Chaihu) or B. chinense(Bei Chaihu) and to investigate their effects on the changes of endogenous metabolites in rats. MethodsChronic unpredictable mild stress (CUMS) procedure was conducted for four weeks and CUMS rat model was established. At the beginning of the week 3, Venlafaxine (0.05 g/kg), XYP (Nan) and XYP(Bei) (46 g/kg) were given tothe CUMS rats,respectively once daily for two weeks. The ethology symptoms of rats were observed and 1H-NMR method was carried out to analyze the changes of metabolites in serum of rats after drug administration. Results Both XYP (Nan and Bei) and Venlafaxine showed the significant influence on the behavioral indicators of CUMS rats compared with the model group (P< 0.05, 0.01). After drug administration, both XYP (Nan and Bei) and Venlafaxine could significantly increase the levels of isoleucine, trimetlylamine oxide, and sinkaline, and decrease those of lactic acid, N-acetyl glycoprotein, creatine, threonine, and β-glucose compared with the model group (P< 0.05, 0.01). Conclusion Chaihu from different sources has the significant antidepressive effect, while XYP (Nan) exerts slightly better efficacy and shorter onset time than XYP (Bei). However, there is no statistical difference. XYP has better accuracy and sensitivity on the antidepression according to the combination of behavior and metabonomic methods.
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[基金项目]
国家自然科学基金资助项目(31070295,81102833);国家重大新药创制科技重大专项课题(2012ZX09103201-035);国家国际科技合作计划项目(2011DFA32630)