中国中药杂志

2021, v.46(19) 4993-5004

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基于代谢组学探究炮制与配伍对四逆散抗抑郁作用的贡献
Roles of processing and compatibility in antidepression of Sini Powder:a metabonomics study

张雅婷;蔡皓;段煜;裴科;莫子晴;钮敏洁;段奕辰;
ZHANG Ya-ting;CAI Hao;DUAN Yu;PEI Ke;MO Zi-qing;NIU Min-jie;DUAN Yi-chen;School of Pharmacy, Nanjing University of Chinese Medicine;Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine;Institute of Chinese Medicine and Food Engineering, Shanxi University of Traditional Chinese Medicine;

摘要(Abstract):

基于UHPLC-Q-TOF-MS的代谢组学技术研究四逆散抗抑郁作用机制,并探讨炮制与配伍对四逆散抗抑郁作用的贡献。除正常组外,其余各组(模型组、柴胡组、白芍组、柴胡-白芍药对组、四逆散组、含醋炙柴胡和醋炙白芍的四逆散组)均采用慢性不可预期温和应激的方法诱导抑郁模型。造模后以9.6 g·kg~(-1)的剂量持续灌胃给药8 d(模型组与正常组大鼠同时灌胃给予等体积的生理盐水)。末次给药后,收集各组大鼠血浆样本,鉴定差异性代谢物并分析代谢通路。该研究共筛查出16种生物标志物。这些发生显著变化的代谢物涉及氨基酸代谢、磷酸戊糖途径、甘油磷脂代谢、鞘脂类代谢、嘌呤代谢等生物代谢通路。大鼠灌胃给药后,一些标志物的水平向正常状态回调。基于炮制与配伍的进一步比较,发现含醋炙柴胡和醋炙白芍的四逆散组在总代谢通路的调节数量上最多。与柴胡和白芍的单味药相比,柴胡和白芍配伍形成的药对显著增加了磷酸戊糖途径及嘌呤代谢的回调;与四逆散相比,含醋炙柴胡和醋炙白芍的四逆散增加了精氨酸的生物合成、嘧啶代谢及磷酸戊糖途径的回调。结果表明四逆散可能是通过调节脂代谢和核苷酸代谢来干预抑郁症。炮制与配伍在一定程度上通过调节核苷酸代谢、能量代谢及氨基酸代谢来增强对抑郁症状的干预作用。
The antidepressant mechanism of Sini Powder was investigated by metabonomics based on UHPLC-Q-TOF-MS, and the roles of processing and compatibility in the antidepression of Sini Powder were discussed in the present study. The chronic unpredictable mild stress(CUMS) model of depression was induced in the model group, the Bupleuri Radix group, the Paeoniae Radix Alba group, the herb-pair group(Bupleuri Radix-Paeoniae Radix Alba), the Sini Powder group, and the vinegar-processed Sini Powder group(Bupleuri Radix and Paeoniae Radix Alba were vinegar-processed). After the establishment of the model, the rats in each group were continuously administered with corresponding drugs(ig) at a dose of 9.6 g·kg~(-1) for eight days [the rats in the model group and the normal group(without model induction) received the same volume of normal saline at the same time]. Following the last administration, the differential metabolites were identified to analyze metabolic pathways based on the rat plasma samples collected from each group. A total of sixteen potential biomarkers were identified. The metabolites with significant changes were involved in many biological metabolic pathways, such as amino acid metabolism, pentose phosphate pathway, glycerol phospholipid metabolism, sphingolipid metabolism, and purine metabolism. After drug intervention, some biomarkers returned to normal levels. Further comparisons of processing and compatibility revealed that the vinegar-processed Sini Powder group had the most total metabolic pathways where differential metabolites were returned to normal. Compared with the individual herbs, the herb-pair significantly improved the recovery of differential metabolites in the pentose phosphate and purine metabolic pathways. Compared with the Sini Powder, the vinegar-processed Sini Powder facilitated the recovery of differential metabolites in the arginine biosynthesis, and pyrimidine and pentose phosphate metabolic pathways. As indicated by the results, Sini Powder may interfere with depression by regulating lipid and nucleotide metabolisms. The processing and compatibility of Chinese herbal medicines can potentiate the intervention on depression by regulating nucleotide, energy, and amino acid metabolisms to a certain extent.

关键词(KeyWords): 抑郁症;四逆散;代谢组学;中药炮制;配伍;UHPLC-Q-TOF-MS
depression;Sini Powder;metabonomics;Chinese herbal medicine processing;compatibility;UHPLC-Q-TOF-MS

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81673600);; 江苏省研究生科研创新计划项目(KYCX20_1604,KYCX18_1637)

作者(Author): 张雅婷;蔡皓;段煜;裴科;莫子晴;钮敏洁;段奕辰;
ZHANG Ya-ting;CAI Hao;DUAN Yu;PEI Ke;MO Zi-qing;NIU Min-jie;DUAN Yi-chen;School of Pharmacy, Nanjing University of Chinese Medicine;Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine;Institute of Chinese Medicine and Food Engineering, Shanxi University of Traditional Chinese Medicine;

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