基于SIRT1/PGC-1α通路介导的线粒体能量代谢研究抑郁症肝郁脾湿病机的生物学实质及中药调控机制

Depression has become a serious social problem. Clinical practices show that the extreme fatigue and multi-system symptoms in depression are highly consistent with characteristics of mitochondrial damage. During the completed national natural science foundation project and the preliminary experiment ,mitochondrial structural damage was found in rats with depression which belongs to stagnation of Liver qi and Spleen dampness , and protected by Chinese medicine prominently. Modern researches suggest that the dysfunction of mitochondrial energy metabolism mediated by SIRT1 / PGC-1α signaling pathway is an important pathological mechanism of depression. Further whether it is the biological essence of pathogenesis of stagnation of Liver qi and Spleen dampness remains to be revealed. Combining with the method of CUS and genetic engineering technology,this project will establish rat model of depression which belongs to stagnation of Liver qi and Spleen dampness, and observe the change of mitochondrial energy metabolism mediated by SIRT1/PGC-1α signaling pathway in hippocampus and skeletal muscle and regulatory mechanism of Chinese medicine in order to reveal the common biological essence.Moreover, the model is established by adopting corticosterone to incubate PC12 cells. SIRT1 inhibitor and PGC-1α siRNA transient transfection method is used to reveal the regulatory mechanism of Chinese medicine on SIRT1 / PGC-1α signaling pathway and its targets.We look forward to clarify that the dysfunction of mitochondrial energy metabolism mediated by SIRT1 / PGC-1α signaling pathway is the biological essence of depression which belongs to stagnation of Liver qi and Spleen dampness and provide a new theory evidence and effective prescription of Chinese Medicine for the prevention and treatment of depression.

抑郁症已成为突出的社会问题。临床发现抑郁症患者的极度疲劳和多系统症状与线粒体损伤特征高度吻合。在已完成的国自然课题和预实验均证实肝郁脾湿抑郁大鼠存在线粒体结构损伤，且中药保护作用明显。研究提示SIRT1/PGC-1α通路介导的线粒体能量代谢异常是抑郁症重要的病理机制，那么其是否为抑郁症肝郁脾湿病机的生物学实质亟待揭示。本项目拟分别采用慢性不可预见应激和基因工程技术建立肝郁脾湿抑郁大鼠模型，观察海马、骨骼肌SIRT1/PGC-1α通路介导的线粒体能量代谢变化及中药干预效应，以揭示其共性生物学实质；拟采用皮质酮孵育PC12细胞模型，运用SIRT1抑制剂和PGC-1α siRNA瞬时转染法，揭示中药对SIRT1/PGC-1α通路的调控机制及作用靶点。期待阐明SIRT1/PGC-1α通路介导的线粒体能量代谢异常是肝郁脾湿抑郁症的生物学实质，为中医药防治抑郁症提供新的理论依据和有效方药。

抑郁症已成为突出的社会问题。临床发现抑郁症患者的极度疲劳和多系统症状与线粒体损伤特征高度吻合。在已完成的国自然课题和预实验均证实肝郁脾湿抑郁大鼠存在线粒体结构损伤，且中药保护作用明显。研究提示SIRT1/PGC-1α通路介导的线粒体能量代谢异常是抑郁症重要的病理机制。本项目采用慢性不可预见应激建立肝郁脾湿抑郁大鼠模型，观察海马、骨骼肌SIRT1/PG C-1α通路介导的线粒体能量代谢变化及中药干预效应，揭示其生物学实质；采用皮质酮孵育PC12细胞模型，运用SIRT1抑制剂和PGC-1α siRNA瞬时转染法，揭示中药对SIRT1/PG C-1α通路的调控机制及作用靶点。并进行临床研究进一步验证。阐明SIRT1/PGC-1α通路介导的线粒体能量代谢异常是肝郁脾湿抑郁症的生物学实质，为中医药防治抑郁症提供新的理论依据和有效方药。