基于1H-NMR代谢组学探讨柴胡-白芍药对“疏肝解郁”的代谢调控途径
投稿时间:2020-09-18     点此下载全文
引用本文:李添,李肖,田俊生,高晓霞,秦雪梅,周玉枝.基于1H-NMR代谢组学探讨柴胡-白芍药对“疏肝解郁”的代谢调控途径[J].中国现代中药,2021,23(8):1380-1390
DOI:10.13313/j.issn.1673-4890.20200918002
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作者中文名作者英文名单位中文名单位英文名E-Mail
李添 LI Tian 山西大学 中医药现代研究中心/化学生物学与分子工程教育部重点实验室,山西 太原 030006 The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China  
李肖 LI Xiao 山西大学 中医药现代研究中心/化学生物学与分子工程教育部重点实验室,山西 太原 030006 The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China  
田俊生 TIAN Jun-sheng 山西大学 中医药现代研究中心/化学生物学与分子工程教育部重点实验室,山西 太原 030006 The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China  
高晓霞 GAO Xiao-xia 山西大学 中医药现代研究中心/化学生物学与分子工程教育部重点实验室,山西 太原 030006 The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China  
秦雪梅 QIN Xue-mei 山西大学 中医药现代研究中心/化学生物学与分子工程教育部重点实验室,山西 太原 030006 The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China  
周玉枝 ZHOU Yu-zhi 山西大学 中医药现代研究中心/化学生物学与分子工程教育部重点实验室,山西 太原 030006 The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China  
基金项目:国家自然科学基金项目(81673572);国家“重大新药创制”科技重大专项(2017ZX09301047);山西省“1331”工程协同创新中心项目(1331KCIC);山西省应用基础研究项目(201601D021164);山西省留学人员科技活动择优资助项目(201991)
中文摘要:目的 利用核磁共振氢谱(1H-NMR)代谢组学技术,分析慢性不可预知温和应激(CUMS)抑郁模型大鼠肝脏内源性代谢物的变化,观察柴胡-白芍药对对此的调节作用,分析柴胡-白芍药对疏肝解郁相关的代谢通路。方法 将SD大鼠随机分为对照组、CUMS模型组、阳性药文拉法辛组和柴胡-白芍药对高(CBH)、低(CBL)剂量组。通过抑郁症的传统药效学指标(大鼠体质量、旷场测试、糖水偏爱实验及强迫游泳实验)评价柴胡-白芍药对的药效。采用1H-NMR代谢组学技术结合多元统计分析方法,分析CBH、CBL组大鼠肝脏代谢物的变化,鉴定可靠的生物标志物并进行代谢通路分析。结果 与对照组比较,模型组大鼠药效学指标均有显著变化,即体质量,旷场穿越格数、直立次数,糖水偏爱率降低(P<0.001)及强迫游泳不动时间增加(P<0.001);柴胡-白芍药对能显著改善模型组大鼠的抑郁样行为。1H-NMR代谢组学分析显示,CUMS会使大鼠体内24个代谢物和10条代谢通路紊乱,柴胡-白芍药对能显著回调其中的21个差异代谢物,对其中7条代谢通路产生影响。结论 柴胡-白芍药对能够改善CUMS抑郁模型大鼠的抑郁样症状,可能是通过调节大鼠体内氨基酸代谢和能量代谢等通路实现的。
中文关键词:柴胡-白芍药对  慢性不可预知温和应激模型  核磁共振肝脏代谢组学  抑郁症  疏肝解郁
 
Metabolic Pathways Related to Liver-soothing and Depression-relieving Effect of Bupleuri Radix-Paeoniae Radix Alba Combination: Based on 1H-NMR Metabolomics
Abstract:Objective To analyze the changes of hepatic endogenous metabolites in rats with chronic unpredictable mild stress (CUMS)-induced depression based on 1H-nuclear magnetic resonance (1H-NMR) metabolomics, observe the regulating effect of Bupleuri Radix-Paeoniae Radix Alba combination (CB), and further clarify metabolic pathways related to the liver-soothing and depression-relieving effect of the combination.Methods Rats were randomized into five groups: blank, model, positive control (venlafaxine), high-dose CB (CBH), and low-dose CB (CBL). The conventional pharmacodynamic indicators of depression such as body weight, number of crossings and rearings in open field test, and sucrose preference rate were employed to investigate the efficacy of CB. 1H-NMR was combined with multivariate statistical analysis method to analyze the changes of metabolites in rat liver upon intervention with CBL and CBH. On this basis, key differential metabolites were screened and related metabolic pathways were elucidated.Results Pharmacodynamic indexes of the rats in the model group changed significantly as compared with those in the blank group, as evidenced by the reduction of body weight, number of crossings and rearings in open field test, and sucrose preference rate (P<0.001) and the increase in immobility time in forced swimming (P<0.001). CB can significantly improve the depression-like behaviors of rats in the model group. According to 1H-NMR metabolomics analysis, CUMS affected 24 metabolites and 10 metabolic pathways, and 21 of them can be significantly recovered by CB. Metabolic pathway analysis showed that the CB exerted antidepressant effect through 7 metabolic pathways.Conclusion CB can alleviate the depression-like symptoms of CUMS model rats, which may be related with the metabolic pathways of amino acids and energy in rats.
keywords:Bupleuri Radix-Paeoniae Radix Alba combination  CUMS model  NMR liver metabolomics  depression  soothing liver and relieving depression
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