基于BDNF-GABA信号通路的苍艾挥发油抗抑郁作用机理研究

抑郁症是发病率高、危害大的精神类疾病。基于单胺类神经递质研发的抗抑郁药有效性和安全性欠佳，亟待研发新型抗抑郁药。申请人根据其临床经验方研制的芳香中药复方制剂苍艾挥发油(CAVO)能改善抑郁患者抑郁症状。大鼠实验证实CAVO可通过鼻-脑通路进入脑内，激活情绪处理相关脑区，上调BDNF和GABA阳性细胞数量，影响神经可塑性，缓解抑郁症状。蛋白组学数据显示其抗抑郁作用可能与BDNF-GABA信号通路的多个靶点相关。为明确CAVO抗抑郁作用机理，项目拟应用神经细胞毒性实验，明确CAVO发挥神经保护作用的活性成分和作用靶点；并应用慢性不可预知应激复制抑郁样大鼠模型，结合基因编辑技术敲除其海马的关键靶点基因，验证发挥抗抑郁作用的CAVO活性成分及BDNF-GABA信号通路的关键作用靶点蛋白。项目有助于阐释中医“芳香解郁”的科学内涵，并为筛选芳香中药复方中的抗抑郁活性成分提供理论依据和研究方向。

Depression is a mental illness with high incidence and great harm. Antidepressants targeting monoamine neurotransmitters have slow onset of action and exhibit low response rates to treatment. It is urgent to develop novel antidepressants. In clinical practice, we have found that aromatic Chinese herbal compound preparation Cang-ai volatile oil (CAVO)can improve depression symptoms of depressed patients, and animal experiments have confirmed that CAVO can enter the rat brain through the nasal-brain pathway, activate the emotion-related brain regions, upregulate the numbers of BDNF- and GABA-positive cells in the corresponding brain regions, affect neuroplasticity and relieve depression. Proteomics results show that its antidepressant effect may be related to multiple targets of the BDNF-GABA signaling pathway. In order to clarify the mechanism of CAVO's anti-depression effect, it is intended to use neurocytotoxicity test, clarify the active ingredients of CAVO and targets of neuroprotection; and apply chronic unpredictable stress to construct the depression-like rat model, knock out the key target genes of its hippocampus with gene editing technology to verify the active ingredients of CAVO and the key target proteins of the BDNF-GABA signaling pathway. This helps to explain the scientific connotation of "aromatic anti-depression" in traditional Chinese medicine, and provides a theoretical basis and research direction for screening new antidepressant drugs in compound aromatic traditional Chinese medicine.