基于NP-cGMP信号通路探讨肝郁脾虚证FD大鼠脑内及胃内发病机制及逍遥散的干预作用

Liver depression-spleen deficiency induced functional dyspepsia (FD) is a typical psychosomatic disease, usually accompanied by anxiety, depression and other emotional disturbance. Studies have shown that FD is closely associated with the brain-gut peptide and neurotransmitter secretion disorder. Natriuretic peptide (NP) is the peptide hormone that coexistence in the nervous system and gastrointestinal. It is closely associated with depression and gastrointestinal motility, however, there is no in-depth study on the relationship between NP-cGMP pathway and Liver depression-spleen deficiency induced FD from the nervous system to the gastrointestinal tract systemically. Our previous study indicated that NP-cGMP signal pathway significantly increased. The effect disappeared when it was pretreated with Xiaoyaosan. NP reduced the number of ICC which is closely related to gastrointestinal motility in liver depression-spleen deficiency induced FD rats. In rat hippocampus, the expression of NP and NPR was increased and brain-derived neurotrophic factor(BDNF) expression was decreased. The gastrointestinal gastric motility was inhibited by Injecting of CNP into hippocampus, which is blocked by Xiaoyaosan. In present study, the brain and gut mechanism of liver depression-spleen deficiency will be investigated based on the NP-cGMP signal pathway and the intervention function of Xiaoyaosan for liver spleen deficiency induced FD rats. From the nervous system to the gastrointestinal tract, from the level of gene to protein, from the level of cell to tissue, reveal the mechanism in the brain and gastrointestinal tract of iver depression-spleen deficiency induced FD rats, expound the may interfere sites on NP-cGMP signaling pathway that the Xiao-yao-san improve FD. Present study provide experimental basis for the further development and clinical application Xiao-yao-san.

肝郁脾虚证功能性消化不良（FD）为典型的心身疾病，常伴抑郁或焦虑等情绪障碍。FD与脑肠肽及神经递质分泌紊乱密切相关，钠尿肽（NP）是共存于脑和胃肠道的神经肽类，NP-cGMP通路与情绪调节及胃肠运动密切相关，目前尚无从脑内到胃肠道深入研究NP-cGMP与肝郁脾虚证FD关系的报道。前期研究发现FD大鼠胃肠道内NP-cGMP通路上调，逍遥散对其有干预作用（WJG2015），NP促使与胃肠起搏密切相关的卡哈尔细胞的丢失而抑制胃动力（PLOSONE2016）。在脑内海马NP及受体表达增多，脑源性神经营养因子下调，海马注射CNP抑制胃运动，逍遥散对其有改善作用。在此基础上本研究拟基于NP-cGMP信号通路探讨肝郁脾虚证FD脑内及胃内发病机制及逍遥散的干预作用。从脑内到胃内，从基因到蛋白水平，从组织到细胞水平揭示肝郁脾虚证FD发病机制，阐明逍遥散的干预作用，为逍遥散进一步开发及临床应用提供实验依据。

肝郁脾虚证功能性消化不良（FD）为典型的心身疾病，常伴抑郁或焦虑等情绪障碍。FD与脑肠肽及神经递质分泌紊乱密切相关，钠尿肽（NP）是共存于脑内和胃肠道的神经肽类，NP-cGMP通路与情绪调节及胃肠运动密切相关，目前尚无从脑内到胃肠道深入研究NP-cGMP与肝郁脾虚证FD关系的报道。通过本研究我们发现FD大鼠胃肠道内NP-cGMP通路上调，逍遥散对其有干预作用，NP促使与胃肠起搏密切相关的卡哈尔细胞的丢失而抑制胃动力。在脑内海马NP及受体表达增多，脑源性神经营养因子下调，海马注射CNP抑制胃运动，逍遥散对其有改善作用。详细阐述了基于NP-cGMP信号通路探讨肝郁脾虚证FD脑内及胃内发病机制及逍遥散的干预作用。从脑内到胃内，从基因到蛋白水平，从组织到细胞水平揭示肝郁脾虚证FD发病机制，阐明逍遥散的干预作用，并深入研究了逍遥散中的芍药的单体芍药苷对胃肠动力的作用机制，为逍遥散进一步开发及临床应用提供实验依据。