愈癫汤治疗精神分裂症的分子及神经影像学机制研究

Schizophrenia is a common serious mental disease, its etiology and pathogenesis is not clear.More and more evidence shows that the onset of schizophrenia is closely related to the altered structure and function of the brain.Traditional Chinese Medicine has a long history of schizophrenia therapy. However, its therapeutic mechanism and target role remains unknown. Our project intends to study the neural and molecular mechanism of "Yu Dian Tang" on schizophrenia, which is based on the theory of "phlegm-blood stasis leading to schizophrenia", with both animal experiments and clinical trials based on our previous studies. Firstly, we will establish experimental Schizophrenia rat models, examined with behavioral, molecular biology and small animal neuroimaging techniques, to investigate the roles of anti-schizophrenia effects of “Yu Dian Tang” in neurological mechanism and imaging changes. Secondly, we will collect and analyze the clinical features of the first onset schizophrenia patients. The brain imaging data will be used for modeling and application of a variety of imaging analysis techniques to study the effect of "Yu Dian Tang" in treatment or improvement in the symptoms of schizophrenia patients. Furthermore, the therapeutic effect and the neurological mechanisms will be investigated. Meanwhile, multiple methods, such as symptom patterns, behaviors, morphology, and molecular biology and so on, will be used in this project. Our research will comprehensively study the mechanism of anti-schizophrenia in traditional Chinese medicine from both holistic and micro levels in order to provide reliable and systematic experimental evidence and preclinical evidence for the clinical application of traditional Chinese medicine prescriptions, which affords traditional Chinese medicine systematically experimental foundation for further exploitation. And to explore a non-invasive clinical diagnostic or examination method for schizophrenia, which diagnostic significance is clear and convenient for clinical application.

精神分裂症是一种常见的重性精神疾病，其病因与发病机制尚不明确。越来越多的证据显示，精神分裂症发病与其大脑结构及功能异常密切相关。中药治疗精神分裂症历史悠久，然其治疗机制与作用靶点目前仍未知。本项目拟在前期研究工作基础上，基于精神分裂症“痰瘀致病”理论，探寻“愈癫汤”治疗精神分裂症的神经及分子机制。即通过建立精神分裂症实验动物模型，结合行为学、分子生物学以及小动物神经影像学技术，研究“愈癫汤”抗精神分裂症的神经分子机制及影像学变化；同时采集分析精神分裂症“首发病”患者临床特征和脑部影像数据，并建模和应用多种影像学分析技术，研究“愈癫汤”治疗或改善精神分裂症患者症状的神经影像学机制。本项目将从整体和微观两个层面全方位研究该方药抗精神分裂的作用机制，以期为其临床推广应用提供可靠、系统的实验依据和临床前期研究证据；并籍此探索一种诊断意义明确，便于临床推广应用的精神分裂症无创性临床诊疗检查方法。

本项目在前期研究工作基础上，基于精神分裂症“痰瘀致病”理论，将基础实验研究与临床试验研究相结合，从行为学、分子生物学、神经生化学，以及多模态神经影像学等层面，探寻愈癫汤治疗精神分裂症的分子及神经影像学机制。通过建立MAM精神分裂症实验模型，结合临床神经影像学分析，观察MAM精神分裂症模型大鼠及精神分裂症患者经愈癫汤干预后，其脑功能区结构、脑功能的改变和神经影像学特点，结合应用现代分子生物学技术，进一步观察愈癫汤对精神分裂症模型大鼠脑区重要信号分子的影响。.研究结果显示，精神分裂症发病与神经发育异常密切相关。愈癫汤可通过减少促炎细胞因子的产生和释放，调节神经炎症及神经递质的变化，作用于Glu-GABA-DA神经递质网络，通过影响神经递质的释放和功能活动，帮助大脑恢复正常的生理功能活动；可通过改变氧化应激与抗氧化应激间的不平衡状态，保护神经细胞膜的功能完整，减轻神经毒性，改善精神分裂症认知功能障碍，影响精神分裂症的发生发展和预后。综合多模态神经影像学特征，经愈癫汤干预后，受试大鼠在多个fMRI指标中存在差异，可透过血脑屏障抑制双侧海马区和前额叶的过度活动，阐明其与精神分裂症发病的相关性。通过对愈癫汤干预治疗精神分裂症患者前后多模态差异脑区与PANSS评分做相关性分析，初步阐明大脑内可能的神经影像学作用靶标，为揭示预测、早期诊断、治疗及评价精神分裂症治疗效果的神经影像学生物标志物奠定重要研究基础。.通过本项目研究，进一步明确了愈癫汤治疗精神分裂症的分子及神经影像学机制，为其临床推广应用提供可靠、系统的实验依据和临床前期研究证据；为新型抗精神病药物治疗的有效性提供一种新的评价手段，有助于寻找治疗靶系统方向；并籍此探索一种诊断意义明确，便于临床推广应用的精神分裂症无创性临床诊疗检查方法。