药学学报, 2021, 56(9): 2403-2409
引用本文:
生宁#, 王彩虹#, 贾志鑫, 王喆, 吴彩胜*, 张金兰*. 代谢组学探索复方二仙汤调节双侧去卵巢大鼠脂代谢紊乱特征[J]. 药学学报, 2021, 56(9): 2403-2409.
SHENG Ning#, WANG Cai-hong#, JIA Zhi-xin, WANG Zhe, WU Cai-sheng*, ZHANG Jin-lan*. The mechanism of Er-xian Decoction in regulating lipid metabolism disorders on bilateral ovariectomized rats based on metabolomics study[J]. Acta Pharmaceutica Sinica, 2021, 56(9): 2403-2409.

代谢组学探索复方二仙汤调节双侧去卵巢大鼠脂代谢紊乱特征
生宁#, 王彩虹#, 贾志鑫, 王喆, 吴彩胜*, 张金兰*
中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050
摘要:
卵巢功能的永久性丧失造成的妇女更年期与脂质代谢紊乱密切相关,复方二仙汤临床上用于多种妇科疾病的治疗,对与卵巢功能的永久性停止有关的疾病有良好疗效,而其作用机制尚未明确。本研究采用代谢组学技术,以双侧去卵巢模型大鼠模拟更年期妇女的生理状态,探索不同绝经阶段脂质代谢特征以及二仙汤调节更年期脂代谢紊乱可能的代谢通路和机制。结果表明,双侧去卵巢模型大鼠发生肝脂代谢异常,与对照组比较,模型组肝脏油红O染色切片发生显著性变化。与模型组比较,复方二仙汤组能显著改善肝脂代谢。动态代谢组学分析结果表明二仙汤对双侧去卵巢模型引起的脂代谢紊乱具有实时调节作用。生物统计学分析找寻得到46个(6个甾体激素、3个鞘酯、11个甘油磷脂和26个甘油酯)血浆潜在生物标志物和32个(1个甾体激素、20个甘油磷脂和11个甘油酯)肝脏潜在生物标志物。分析差异代谢通路并构建了二仙汤显著调节的脂质代谢网络,为深入了解更年期状态下脂代谢紊乱渐进变化和复方二仙汤调节作用特点和机制提供了有价值的信息。研究遵守中国医学科学院药物研究所动物实验伦理委员会制定的规程并通过动物实验伦理审查(No.00000918)。
关键词:    复方二仙汤      代谢组学      双侧去卵巢模型大鼠      脂代谢紊乱     
The mechanism of Er-xian Decoction in regulating lipid metabolism disorders on bilateral ovariectomized rats based on metabolomics study
SHENG Ning#, WANG Cai-hong#, JIA Zhi-xin, WANG Zhe, WU Cai-sheng*, ZHANG Jin-lan*
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
Studies have shown that women's menopause caused by permanent cessation of ovarian function is closely related to lipid metabolism disorders. Er-xian Decoction has been used in the clinical treatment for gynecological diseases and has a good effect on diseases related to reduced sex hormone function. In this study, metabolomics was performed on bilateral ovariectomized model rats within 12 weeks after modeling to mimic the physiological state of menopausal women in different menopausal stages and Er-xian Decoction dosed model rats. The results of liver oil red O staining sections showed lipid metabolic disorder of bilateral ovariectomized model rats and the regulating effects of Er-xian Decoction. 46 potential biomarkers (6 steroid hormones, 3 sphingolipids, 11 phospholipids and 26 glycerides) in plasma and 32 potential biomarkers (1 steroid hormones, 20 phospholipids and 11 glycerides) in liver were obtained based on lipidomics analysis. Then, we analyzed the differential metabolic pathways and construct the lipid metabolism network significantly regulated by Er-xian Decoction. The results provided valuable information for in-depth understanding of the gradual changes on lipid metabolism disorders under menopausal conditions and the characteristics and mechanisms of compound Er-xian Decoction's regulatory effects. The study complied with the procedures established by the Animal Experiment Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and passed the animal experiment ethics examine (No. 00000918).
Key words:    Er-xian Decoction    metabolomics    bilateral ovariectomized model rats    lipid metabolism disorder   
收稿日期: 2021-04-29
DOI: 10.16438/j.0513-4870.2021-0649
基金项目: 中国医学科学院医学与健康科技创新工程(2016-I2M-3-010).
通讯作者: 吴彩胜,E-mail:wucsh@xmu.edu.cn;张金兰,E-mail:zhjl@imm.ac.cn
Email: wucsh@xmu.edu.cn;zhjl@imm.ac.cn
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