Quantitative proteomics reveal antidepressant potential protein targets of xiaochaihutang in corticosterone induced model of depression
Quantitative proteomics reveal antidepressant potential protein targets of xiaochaihutang in corticosterone induced model of depression
复制标题
定量蛋白质组学揭示小柴胡汤在皮质酮诱导的抑郁模型中抗抑郁的潜在蛋白质靶标
DOI：
10.1016/j.jep.2018.11.020
复制
发表时间：
2019
影响因子：
5.4
通讯作者：
Wu Chunfu
中科院分区：
文献类型：
--
作者：
Zhang Kuo;He Meiyao;Su Dongmei;Pan Xing;Li Yuting;Zhang Haotian;Yang Jingyu;Wu Chunfu
民族药理相关性小柴胡汤是治疗少阳症的著名中草药方剂之一，多年来一直成功地用于抑郁症。本实验室已证实，醒脑通对多种抑郁动物模型所致的抑郁行为有明显的缓解作用，但以往的研究多集中在一个或几个蛋白质靶点上，缺乏蛋白质的动态变化和相互关系。因此，潜在的蛋白质靶点和机制还需要进一步的系统研究。目的利用等压标记相对和绝对定量(ITRAQ)分析方法，发现和评价口服XCHT对皮质酮(Cort)诱导的抑郁模型大鼠海马区差异表达蛋白(DEPS)的影响。材料与方法采用两种行为绝望模型(强迫游泳实验和悬尾实验)评价XCHT的抗抑郁作用。用iTRAQ分析方法检测XCHT治疗后大鼠海马区DEPS的变化。通过基因本体论(GO)、京都基因与基因组百科全书(KEGG)和蛋白质-蛋白质相互作用(PPI)网络对潜在的蛋白质靶点和机制进行评估。XCHT处理后共鉴定出241个DEPS，包括68个上调蛋白和173个下调蛋白。GO富集结果表明，XCHT主要调控细胞内参与应激反应的结构蛋白、转移酶活性和类固醇激素。KEGG浓缩分析表明，内吞作用可能是XCHT治疗抑郁症的主要途径。PPI分析预测细胞分裂周期，凋亡调节蛋白1(Ccar1)和Calretinin(Calb2)可能在XCHT的抗抑郁网络中起核心作用。结论XCHT通过恢复DEPS而在抗抑郁作用中发挥重要作用，从而导致海马神经发生、神经递质和类固醇激素的失调。目前的结果希望为揭示XCHT治疗抑郁症的潜在蛋白质靶点提供新的视角。
Ethnopharmacological relevanceXiaochaihutang (XCHT), one of famous Chinese herbal prescription for treating Shaoyang symptom, has been used successfully in depressive disorders for many years. Our laboratory has demonstrated that XCHT remarkably alleviated various depressive behaviors induced by several depressive animal models, but previous studies only focused on one or several protein targets, lacked dynamic change and interrelation of proteins. Therefore, potential protein targets and mechanisms are required further systematic investigation.Aim of the studyTo discover and assess the differentially expressed proteins (DEPs) of hippocampus after oral administration of XCHT in corticosterone (CORT) induced model of depression by using isobaric tags for relative and absolute quantification (iTRAQ) analysis.Materials and methodsThe antidepressant effects of XCHT were assessed by two behavioral despair models (forced swimming test and tail suspension test) in CORT induced model of depression. The DEPs of hippocampus after XCHT treatment were investigated by iTRAQ analysis. Potential protein targets and mechanisms were assessed by gene ontology (GO), Kyoto encyclopedia of gene and genomes (KEGG) and protein-protein interaction (PPI) network.ResultsOur data demonstrated XCHT could significantly improve depressive behaviors. A total of 241 DEPs were identified after XCHT treatment, including 68 up regulation and 173 down regulation proteins. GO enrichment results indicated that XCHT mainly regulated intracellular structural proteins involved in cellular response to stress, transferase activity and steroid hormone. KEGG enrichment analysis showed that endocytosis might be the principal pathway of XCHT on depression. PPI analysis predicted cell division cycle and apoptosis regulator protein 1 (Ccar1) and Calretinin (Calb2) might play the central roles in XCHT's antidepressant network.ConclusionOur results indicate that XCHT plays the important roles in antidepressant action by restoring DEPs, which results in the dysregulation of hippocampal neurogenesis, neurotransmitter and steroid hormone. The current results wish to provide novel perspectives for revealing the potential protein targets of XCHT on depression.