摘要
该研究旨在应用定量蛋白质组学技术探讨交泰丸对慢性不可预知温和刺激(chronic unpredictable mild stress,CUMS)抑郁模型大鼠海马区蛋白表达的影响,进而研究其抗抑郁机制。将SD大鼠随机分为对照组、模型组、交泰丸组及氟西汀组,每组8只。除对照组外,其余3组大鼠进行4周CUMS造模,以建立抑郁模型。连续给药4周后,分析各组大鼠行为学及海马组织病理形态变化。提取海马组织蛋白,运用定量蛋白质组学技术比较各组间差异表达蛋白(differentially expressed proteins,DEPs),并进行生物信息学分析。采用蛋白免疫印迹(Western blot)法验证关键DEPs。结果显示,交泰丸可显著改善CUMS抑郁模型大鼠的抑郁样行为及海马组织病理形态。从大鼠海马组织中共鉴定出5412个蛋白,其中对照组与模型组间有65个DEPs,交泰丸组与模型组间有35个DEPs。交泰丸组与对照组变化趋势相一致的DEPs共有16个,上述DEPs主要涉及鞘脂信号通路、AMPK信号通路及多巴胺能突触等信号通路。此外,Western blot检测各组大鼠海马区Ppp2r2b、Cers1及Ndufv3蛋白,与蛋白质组学结果一致。综上可得,交泰丸可能通过影响Ppp2r2b、Cers1、Ndufv3等蛋白水平,调控鞘脂信号通路、AMPK信号通路及多巴胺能突触,从而发挥抗抑郁作用。
This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills.The SD rats were randomized into control,model,Jiaotai Pills,and fluoxetine groups(n=8).Other groups except the control group were subjected to CUMS modeling for 4 weeks.After 4 weeks of continuous administration,the changes of behavior and pathological morphology of the hippocampal tissue were observed.Proteins were extracted from the hippocampal tissue,and bioinformatics analysis was performed for the differentially expressed proteins(DEPs)identified by quantitative proteomics.Western blot was employed to verify the key DEPs.The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression.A total of 5412 proteins were identified in the hippocampus of rats,including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group.There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group,which were mainly involved in sphingolipid,AMPK,and dopaminergic synapse signaling pathways.The Western blot results of Ppp2r2b,Cers1,and Ndufv3 in the hippocampus were consistent with the results of proteomics.In conclusion,Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b,Cers1,Ndufv3 and other proteins and regulating sphingolipid,AMPK,and dopaminergic synapse signaling pathways.
作者
戴国梁
孙冰婷
陈泽瑀
陈佩瑶
蒋志涛
居文政
DAI Guo-liang;SUN Bing-ting;CHEN Ze-yu;CHEN Pei-yao;JIANG Zhi-tao;JU Wen-zheng(Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China;Department of Pharmacy,Nanjing Hospital of Traditional Chinese Medicine,Nanjing 210022,China;School of Pharmacy,Xuzhou Medical University,Xuzhou 221004,China;Department of Pharmacy,Zhangjiagang Hospital of Traditional Chinese Medicine,Suzhou 215600,China)
出处
《中国中药杂志》
CSCD
北大核心
2023年第23期6500-6508,共9页
China Journal of Chinese Materia Medica
基金
江苏省中医药科技发展计划面上项目(MS2021011)
江苏省基础研究计划面上项目(BK20211394)
江苏省医学重点实验室项目(szdsys09)。
