基于“痰瘀交互”理论的愈癫汤及其拆方对精神分裂症大鼠不同脑区氧化应激损伤及ERK信号转导机制影响的研究

Schizophrenia is a kind of mental disesse with high incidence characterized by change of basic personality, split of thinking, emotion and behavior, disorder between spiritual activities and the external environment. Now western medicine treatment has its limitations, especially on the clinical effect of social disability in patients.But Chinese medicine have good effect and broad prospect in the treatment of it. Recent research showed that Cognition disorders related to Oxidative stress mediated by NO in schizophrenia patients, and the content of NO will reduce caused by the fewer target genes and protein expression of iNOS by prohibiting the activation of ERK signal pathway. We summarized that Yudian Decoction has a good clinical effect in the treatment of Schizophrenia.In this research, we use method of Separated Formulae based on"establishing treating principle according to the mechanism of disease，dividing formula according to the treating principle". We establish the treatment principle of "Eliminating Phlegm - Removing Blood Stasis- Breaking Junction" in view of"Phlegm and Stasis"to give an interpretation of the essence on treatment and syndrome differentiation on schizophrenia .On this basis,to explore the different functions of Yudian Decoction and its Separated Formulae, and the influence on cognitive function to different modern medicine indexes in the view of Signal Pathway Mediated by ERK - NO - Oxidative stress.Then We expect that this research will lay a theoretical foundation for the further study of syndrome-treatment essential for Schizophrenia treated by Chinese medicine and will provide a more effective clinical treatment method.

精神分裂症是以患者基本个性改变，思维、情感与行为的分裂，精神活动与外界环境不协调为主要特征的一种高发性精神疾病。目前西药治疗有局限性，对社会功能缺陷疗效较差，而中药治疗已显示出极大优势。研究表明精神分裂症患者认知功能缺损与NO介导的氧化应激有关，通过抑制ERK信号转导途径的活化，可以抑制iNOS靶基因和蛋白的表达，进而控制NO产量。课题组前期工作基础表明愈癫汤治疗本病临床疗效显著，本研究依据"法依病机、拆方依法"原则，根据不同功效采用拆方研究方法，从痰、瘀入手，确立"消痰化瘀，破结行气"为治则，诠释精神分裂症"痰瘀互结"中医辨治实质，并以此为基础从现代医学ERK信号转导通路-NO-氧化应激损伤角度，探寻愈癫汤及其拆方在不同现代医学指标方面的作用及其对精神分裂症动物模型认知功能方面的影响，以期为深入探讨本病中医药治疗证治实质奠定理论基础，并提供更为有效的临床治疗手段。

项目背景：精神分裂症属重性精神障碍，其病因及发病机理可能与抗氧化防御系统、氧自由基及NO信号通路为主的氧化应激反应导致的多巴胺功能亢进及谷氨酸功能紊乱密切相关。中医神志病学理论认为精神分裂症的病位在脑，主要病理因素与痰、瘀密切相关，核心病机为痰瘀互结而致脑神受损，体用失和。基于癫狂病“痰滞脑神”理论而化裁的愈癫汤，在临证中取得了确切疗效。.主要研究内容：采用MORRIS水迷宫、分光光度计法、酶联免疫法、RT-PCR法及WB法等研究方法，探讨愈癫汤及其拆方对精神分裂症模型大鼠海马、下丘脑及额前组织抗氧化防御系统、氧自由基、NO信号通路、p-ERK-BDNF信号转导通路及对中枢神经系统的影响。.重要结果：愈癫汤及其拆方可以正性调节精神分裂症模型大鼠海马、下丘脑及额前组织抗氧化防御系统、氧自由基及NO信号通路，从“p-ERK-BDNF信号转导通路-NO-氧化应激损伤”角度阐明愈癫汤及其拆方治疗精神分裂症“消痰化瘀、破结行气”的中医证治实质，为临床应用愈癫汤及其拆方治疗精神分裂症提供实验依据，充实本方药理学基础。