课题组前期研究表明，经典古方开心散通过多靶点调控抑郁相关分子通路发挥抗抑郁作用，其成药制剂参志苓片在治疗轻/中度抑郁症临床试验中表现出明显的治疗优势，发现参志苓治疗后抑郁症患者血浆中多个miRNAs的表达水平发生显著变化，并进一步筛选目标miRNA及预测了相关靶基因。本项目结合miRNA转录后调控参与抑郁症发生发展进程的最新研究进展，在前期抗抑郁临床及临床前研究成果的基础上，拟基于蛋白质组学和miRNA转录组学多组学联合的系统生物学研究方法，筛选参志苓治疗前后抑郁症患者血浆中差异表达的miRNAs及蛋白质，并对差异miRNAs和蛋白进行生物信息学分析及验证；建立与抑郁症发病机制及参志苓抗抑郁相关的miRNAs-mRNA-蛋白质调控轴/网络，并在细胞水平和动物水平进行验证和深入的生物学功能研究；综合上述研究结果，最终在转录后及翻译后多个层面系统阐释参志苓抗抑郁的分子网络。

Our previous study shows that the traditional Kai-xin San exhibits anti-depression effect by interacting with multiple targets in the molecular pathway of depression. Its tablet formulation Shenzhiling exhibits high efficacy in the clinical treatment of patients with mild to moderate depression. We have demonstrated that the expression levels of several plasma miRNAs vary greatly after the treatment. Moreover, we have identified target miRNAs and predicted the related genes. In this proposal, based on the most recent advances in the study of miRNA in depression patients and preclinical and clinical investigation, we plan to analyze and identify the differentially expressed miRNAs and proteins in depression patients before and after Shenzhiling treatment. System biology techniques of proteomics and transcriptomics will be utilized. The miRNA-mRNA-protein networks and regulation axis related to the pathogenesis of depression and the treatment effect of Shenzhiling will be constructed and further investigated on the cellular and body levels. Based on these results, the molecular networks involved in the anti-depression activity of Shenzhiling will be described in the aspects of gene transcription and translation.