基于肝脏蛋白质组学探讨加味丹栀逍遥散的抗抑郁作用及机制

摘要:

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[目的]探讨加味丹栀逍遥散对慢性不可预知性温和应激(CUMS)抑郁小鼠模型的干预作用及可能机制.[方法]C57BL/6N小鼠分为正常组、模型组、加味丹栀逍遥散组和氟西汀组.采用CUMS复制抑郁模型,模型成功后灌胃给药4周.末次给药后进行行为学测试,采用串联质谱标签法(TMT)蛋白质组学分析小鼠肝脏差异蛋白的表达谱,通过Kyoto encyclopedia of genes and genomes(KEGG)通路富集加味丹栀逍遥散抗抑郁的相关通路和蛋白;血液生化检测总胆固醇及总胆汁酸含量.[结果]与正常组相比,模型组小鼠糖水偏好率下降,自主活动次数减少,加味丹栀逍遥散给药后上调小鼠糖水偏好率及自主活动次数.蛋白组学结果显示模型组与加味丹栀逍遥散给药组之间肝脏差异表达蛋白20个,其中上调11个,下调9个.KEGG通路富集分析发现差异表达蛋白主要参与了胆固醇代谢、初级胆汁酸的合成等.生化检测发现,与正常组相比,模型组总胆固醇含量下降而胆汁酸含量升高,加味丹栀逍遥散给药能显著增加总胆固醇含量而减少总胆汁酸含量.[结论]加味丹栀逍遥散具有良好的抗抑郁效应,其机制可能与调节肝脏胆固醇异常代谢、降低血液总胆汁酸有关.

[Objective]To investigate the interventional effects and possible mechanisms of modified Danzhi Xiaoyao San on chronic unpredictable mild stress(CUMS)depression mouse model.[Method]Forty C57BL/6N mice were divided into the normal,the model,the fluoxetine,and modified Danzhi Xiaoyao San groups,10 mice in each group.The depression model was successfully replicated by CUMS for 8 weeks,and then all the mice were administered by gavage for 4 weeks.After the final administration,behavioral tests were performed;the expression profiles of the differential proteins in the mice liver were analyzed by tandem mass spectrometry tagging(TMT)proteomics;the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway were used to enrich the antidepressant pathways and proteins associated with modified Danzhi Xiaoyao San.The total cholesterol and total bile acids in mice were analyzed by blood biochemistry.[Result]The behavioral results showed that the sugar preference rate decreased(P<0.05)and the locomotor activity times decreased(P<0.05)in the model group compared with the normal group;compared with the model group,the sugar preference rate and the locomotor activity times were significantly increased(P<0.05,P<0.05)in the modified Danzhi Xiaoyao San group.The proteomic results showed a total of 20 DEPs in the liver between the model and the modified Danzhi Xiaoyao San groups,of which 11 were up-regulated and 9 were down-regulated.The KEGG pathway enrichment analysis revealed that the DEPs were mainly involved in cholesterol metabolism,primary bile acid synthesis,etc..Compared with the normal group,the total cholesterol content of the model group decreased significantly while the bile acid content increased significantly,and the total cholesterol content of the model group increased significantly while the total bile acid content decreased with the administration of modified Danzhi Xiaoyao San.[Conclusion]The modified Danzhi Xiaoyao San has good antidepressant effects and its antidepressant mechanisms may be related to the regulation of abnormal cholesterol metabolism and the reduction of total blood bile acids.

作者:

汪保英 李雅静 田磊 刘辉 白明 栗俞程 许二平

Wang Baoying;Li Yajing;Tian Lei;Liu Hui;Bai Ming;Li Yucheng;Xu Erping(Academy of Chinese Medical Sciences,Henan University of Chinese Medicine,Zhengzhou 450046,China;School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区:

河南中医药大学中医药科学院

出处:

《河南师范大学学报(自然科学版)》 CAS  2024年第1期150-156,I0017,共8页

Journal of Henan Normal University(Natural Science Edition)

基金:

国家自然科学基金(81973739,82274496) 河南省优秀青年科学基金(202300410249) 河南省科技攻关项目(222102310233)。

关键词:

抑郁症 蛋白组学 加味丹栀逍遥散 肝郁 胆汁酸

depression proteomics modified Danzhi Xiaoyao San liver stagnancy bile acids

分类号:

R285.5 [医药卫生—中药学] 

基于肝脏蛋白质组学探讨加味丹栀逍遥散的抗抑郁作用及机制.pdf