基于抑郁症PFC-NAc-VTA神经环路与下丘脑摄食相关信号的中枢外周效应研究“肝郁犯胃”的发生机制

中医认为肝郁日久，影响及胃，形成肝郁犯胃证；抑郁症常常引起胃肠动力障碍。在病因、临床表现方面，中医肝郁与抑郁症PFC-NAc-VTA神经环路相互投射失调导致的快感缺失相似；中医肝郁犯胃与抑郁症出现下丘脑摄食相关信号变化及胃动力障碍相似。课题以此为切入点，从抑郁症PFC-NAc-VTA神经环路与下丘脑摄食相关信号的中枢外周效应观察“肝郁犯胃”发生机制。课题采用慢性心理应激加孤养法制作抑郁模型，应用行为学、 HPLC、Western Blot、ELISA、RT-PCR等方法，动态观察PFC-NAc-VTA神经环路DA、GABA和Glu等神经递质及突触可塑性变化，下丘脑摄食信号ghrelin、orexin、CCK、NPY、leptin及其受体mRNA变化，以及疏肝和胃汤的影响。研究将为揭示“肝郁犯胃”的神经-内分泌机制，研发疏肝和胃中药提供实验依据，并为深入研究中医脏腑之间的相互传变奠定基础。

TCM regards that chronic liver-qi depression can influence stomach, which in turn develops syndrome of stomach disorder induced by liver-qi depression. Depression often causes gastrointestinal motility disorders. In the aspects of etiology, clinical symptoms, TCM symptom of liver depression is similar to the anhedonia caused by mutual projection disorders of Depression PFC-NAc-VTA neural circuit; TCM syndrome of stomach disorder induced by liver-qi depression is also similar to peripheral gastric motility disorders, as well as the changes of feeding-related signals in hypothalamic. As a breakthrough point, the purpose of this research is to study the mechanism of syndrome of stomach disorder induced by liver-qi depression, based on central and peripheral effect of Depression PFC-NAc-VTA neural circuit and feeding-related signals of hypothalamic. The research is to dynamically observe the changes of neurotransmitter (DA, GABA, Glu) and synaptic plasticity in PFC-NAc-VTA neural circuit, feeding-related signals (ghrelin, orexin, CCK, NPY, leptin, containing receptors mRNA ) in hypothalamic, and the effect of Shugan Hewei Decoction, applied advanced methods, including behaviorstics, HPLC, Western Blot, ELISA, RT-PCR, adopted the model rats which were made by the method of chronically psychological stress and separately raised. The research will provide the experimental basis, which reveals the nerve - endocrine mechanism of syndrome of stomach disorder induced by liver-qi depression, as well as to provide experimental basis for developing Chinese patent medicine to sooth liver and harmonize stomach, and lay the theoretical and profound foundation for studying transmission of TCM Zang and Fu mutual disease.