基于大脑皮层lncRNA DANCR调控miR-200表达研究逍遥散干预抑郁症的分子机制

抑郁症是全球发病率最高的精神类疾病，发病机制不明。近年来发现lncRNA能影响神经可塑性，在许多精神类疾病中存在异常表达。但目前lncRNA与抑郁症的相关性研究相对较少。课题组前期研究发现：逍遥散通过调控lncRNA DANCR及miR-200，能抑制神经元损伤，缓解抑郁症行为学及生物学异常。由此我们提出逍遥散通过DANCR干预抑郁症新机制：逍遥散中有效成分通过影响DANCR表达，基于ceRNA调控机制吸附互补的miR-200，导致下游相关信号通路被激活，产生干预抑郁症的作用。本研究① 拟通过体内外实验证实DANCR功能，获得DANCR抑制miR-200表达从而激活下游相关信号通路的可靠研究证据；② 拟通过对大脑皮层代谢产物进行分析，研究逍遥散通过DANCR干预抑郁症的物质基础；为抑郁症诊断及防治提供理论参考，为中医复方逍遥散的干预抑郁症的作用机制提供实验依据。

The incidence of depression is the highest among all the mental illnesses in the world, and the pathogenesis of which is not fully understood. In recent years, increasing evidences indicated that long non-coding RNA (lncRNA) is involved in modulation of neuroplasticity. And the abnormal expression of lncRNA was detected in various mental illnesses. However, relatively few studies focused on the relationship between lncRNA and depression. According to the multi-omics studies and molecular biology evidences of rats cerebral cortical neurons, we found that xiao-yao-san can alleviate nerve injury and prevent depression relapse by promoting lncRNA DANCR expression and repressing miR-200 expression. We thus proposed a new mechanism that the active component in xiao-yao-san can modulate the expression of DANCR. Given the ceRNA regulation mechanism, when DANCR binds with miR-200 directly, DANCR will upregulate the expression of miR-200 targeting genes. As the results, the downstream signaling pathways of miR-200 wiil be activate, leading to the alleviation of depressive symptoms. The current study is aimed to ① exploring the role of DANCR in xiao-yao-san mediated inhibition of depression, ② and analyzing the metabolites of xiao-yao-san in cerebral cortex. These results will provide theoretical evidence for prevention and treatment of depression, and provides experimental basis for the mechanism study of xiao-yao-san.