基于转录组学和蛋白组学的蒙药高尤-13味丸调控HPA轴治疗慢性应激大鼠抑郁症机制探讨

Depression seriously affects people's physical and mental health, although the new anti-depression drugs are one after another, there are still various degrees of adverse reactions and side effects. The anti-depressant effect of Gaoyou-13 (G-13) in previous study was good in clinic without obvious side effects. The study found that G-13 can improve the behavioral abnormalities of depression rats and inhibit neuronal apoptosis of hippocampus caused by chronic stress, and is closely related to the regulation of HPA axis in depressive model rats. The specific mechanism has not been elucidated. In this study, we prepared depression rat model by chronic stress and re-validated the effect of G-13 on depression rats. RNAseq and iTRAQ techniques were used to study the molecular mechanisms of G-13 in treating HPA axis tissue (hypothalamus, pituitary gland and adrenal gland) of rats with chronic stress depression . The results were analyzed by bioinformatics-related software, and were verified by modern molecular biology techniques. The effect mechanisms of Mongolian medicine G-13 on HPA axis in treating chronic stress depression were discussed, which provide experimental basis for .depression.

抑郁症严重影响人们身心健康，虽然抗抑郁症新药层出不穷，但仍存在不同程度的不良反应和毒副作用。前期研究工作证实蒙药高尤-13味丸（G-13）临床抗抑郁症疗效好，无明显毒副作用，研究发现G-13能改善抑郁模型大鼠行为学异常及抑制慢性应激造成的大鼠海马神经元凋亡而发挥抗抑郁作用，并且与调控抑郁模型大鼠下丘脑-垂体-肾上腺皮质（HPA）轴密切相关，具体机制尚未阐明。本课题采用慢性应激抑郁模型制备大鼠抑郁症模型并再次验证G-13抗大鼠抑郁症作用；采用RNAseq技术和iTRAQ技术对G-13治疗慢性应激抑郁模型大鼠的HPA轴组织(下丘脑、垂体、肾上腺)进行分子机理研究；采用生物信息学相关软件对上述结果进行互作分析，并采用现代分子生物学技术对分析结果进行验证，探讨蒙药G-13治疗慢性应激抑郁症过程中对HPA轴的作用机制，为蒙药G-13治疗抑郁症提供实验依据。

抑郁症严重影响人们身心健康，虽然抗抑郁症新药层出不穷，但仍存在不同程度的不良反应和毒副作用。蒙药高尤-13味丸（G-13）治疗抑郁症疗效确切。我们利用免疫组织化学、Western blotting、RT-PCR蛋白质组学等对蒙药高尤-13味丸（G-13）对大鼠抑郁症的治疗机制进行了探讨，表明蒙药高尤-13味丸（G-13）可通过改善大鼠抑郁状态，逆转抑郁症中大鼠体重、糖水偏爱率等作用治疗抑郁症。但是作用靶点和分子机制还有待于深入阐明。系统生物学的的出现为中药复方作用机制评价提供了全新的思路，本课题拟采用DIA定量蛋白组方法，阐明蒙药复方高尤-13味丸（G-13）的药理作用机制，解析复方蒙药高尤-13味丸（G-13）对于抑郁症的药物作用靶点，为蒙药复方的机制研究探索新的途径。