中国中药杂志2025，Vol.50Issue(16)：4510-4524,15.DOI:10.19540/j.cnki.cjcmm.20250409.701
整合血清代谢组学和肠道菌群分析研究酸枣仁提取物改善睡眠剥夺大鼠抑郁样行为的药效作用
Antidepressant effects of Ziziphi Spinosae Semen extract on depressive-like behaviors in sleep deprivation rats based on integrated serum metabolomics and gut microbiota
摘要
Abstract
Based on serum metabolomics and gut microbiota technology,this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW)and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO)in improving depressive-like behaviors induced by sleep deprivation.A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation.Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test.The expression of barrier proteins,such as Occludin,in the colon was determined by immunofluorescence.UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats,screen for differential metabolites,and analyze metabolic pathways.The diversity of the gut microbiota was detected using 16S rRNA gene sequencing.Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota.The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats.A total of 34 differential metabolites were identified through serum metabolomics.SZRW and SZRO shared five metabolic pathways,including phenylalanine metabolism.SZRW uniquely featured taurine and hypotaurine metabolism,while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism.Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila,promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1,Occludin,and Claudin-1.SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species.Both SZRW and SZRO can regulate endogenous metabolism,including amino acids,energy,and lipids,alter the gut microbiota microecology,and improve depressive-like behaviors.SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW.The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.关键词
酸枣仁/水提物/石油醚提取物/睡眠剥夺/抑郁样行为/血清代谢组学/肠道菌群Key words
Ziziphi Spinosae Semen/aqueous extract/prtroleum ether extract/sleep deprivation/depressive-like behaviors/serum metabolomics/gut microbiota引用本文复制引用
宋良蕾,孙亚禹,牛泽佳,刘嘉颖,裴香萍,闫艳,杜晨晖..整合血清代谢组学和肠道菌群分析研究酸枣仁提取物改善睡眠剥夺大鼠抑郁样行为的药效作用[J].中国中药杂志,2025,50(16):4510-4524,15.基金项目
山西省科学技术厅山西省科技创新人才团队项目(202304051001020) （202304051001020）
山西省科技成果转化引导专项计划项目(202204021301063) （202204021301063）
山西省科学技术厅中央引导地方科技发展资金项目(YDZJSX2021C025) （YDZJSX2021C025）
山西省中医药重点研究室建设项目(zyyyjs2024024) （zyyyjs2024024）
山西省中医药管理局中医药创新团队项目(zyytd2024026) （zyytd2024026）
山西中医药大学科技创新团队项目(2022TD2009) （2022TD2009）
山西中医药大学2024年度科技创新能力培育计划项目(2024PY-JL-11-01,2024PY-JL-11-02) （2024PY-JL-11-01,2024PY-JL-11-02）
