银杏叶提取物对慢性社交挫败应激小鼠外周血清代谢物的调控作用  

Regulatory Effects of Ginkgo biloba Extract on Peripheral Serum Metabolite Profile of Mice with Depression-like Behavior

作　　者：张学丽[1] 蔡晓莹 厉伟兰[1] 郑啸 ZHANG Xue-li;CAI Xiao-ying;LI Wei-lan;ZHENG Xiao(Department of Pharmacy,Zhongda Hospital,Southeast University,Nanjing 210009,China;School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China;Key Laboratory of Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]东南大学附属中大医院药学部,南京210009 [2]中国药科大学药学院,南京210009 [3]中国药科大学药物代谢动力学重点实验室,南京210009

出　　处：《中国药学杂志》2021年第7期546-552,共7页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金面上项目资助(81973556);江苏省科教强卫青年医学重点人才项目资助(QNRC2016811)。

摘　　要：目的探讨银杏叶提取物对慢性社交挫败应激小鼠抑郁样行为的影响,并分析其对抑郁模型小鼠外周血清代谢谱的影响。方法采用慢性社交挫败应激造模10 d诱导小鼠抑郁样行为,给药组预防性给予氟西汀(15 mg·kg^(-1))或银杏叶提取物(低剂量组:120 mg·kg^(-1),高剂量组:240 mg·kg^(-1))。于第11天通过社交躲避和旷场实验进行行为学评价,收集小鼠外周血清并采用非靶向代谢组学方法考察代谢谱的变化。结果与模型组小鼠相比,银杏叶提取物给药后可显著延长抑郁小鼠在社交区停留时间,提高社交得分。银杏叶提取物可显著转归外周血清中色氨酸、次黄嘌呤、黄嘌呤、氧化型谷胱甘肽、黄嘌呤核苷酸、肌苷三磷酸水平的异常。结论银杏叶提取物可缓解慢性社交挫败应激抑郁小鼠抑郁样行为,对其外周血清中次黄嘌呤和肌苷三磷酸的水平有明显调控作用。OBJECTIVE To investigate the effects of Ginkgo biloba extract on chronic social defeat stress-induceddepression-like behavior in mice,and explore its effect on peripheral serum metabolic profile.METHODS Mice were subjected to chronic social defeat stress(CSDS)for 10 d,and were given fluoxetine(15 mg·kg^(-1))or Ginkgo biloba extract(120,240 mg·kg^(-1))as a preventive treatment.On the 11 th day,social avoidance test and open field test were conducted for behavioral evaluation.Peripheral serum was collected and potential metabolic changes were screened by untargeted metabolomics assay.RESULTS The mice from the Ginkgo biloba extract treatment group showed significantly longer stay time in the social area and the social score was improved.Ginkgo biloba extract treatment significantly reduced the levels of tryptophan,hypoxanthine,xanthine,oxidized glutathione,xanthine nucleotide and inosine triphosphate in the peripheral serum of CSDS mice.CONCLUSION Ginkgo biloba extract can alleviate depression behavior in mice with chronic social defeat stress.The antidepressant efficacy of Ginkgo biloba extract is closely related to the regulation of hypoxanthine and inosine triphosphate in peripheral serum.

关 键 词：银杏叶提取物 抑郁样行为 慢性社交挫败应激 代谢标志物 

分 类 号：R965[医药卫生—药理学]