母鼠孕前肝疏泄失常对雄性子代行为及神经生化的影响

Our and related researches have shown that the parent generation with liver failing to convey and disperse have a negative impact on the behaviors of their offsprings. Furthermore, it is related with the high incidence of affective disorders of their offsprings. From typical anger, depression abnormal emotions caused by two subtypes of liver failing to convey and disperse (PMS Liver-qi invasion、PMS Liver-qi depression) start, Researching and revealing the effects of maternal rats with liver failing to convey and disperse on the behaviors and neurobiochemistry of their adult offsprings, is the key scientific issues of probing the mechanism of the occurrence of liver failing to convey and disperse. We are intend to adapt the technology of CMS and RIT to induce maternal pregnancy liver failing to convey and disperse, observing the behavior and neurochemistry change of adult male offsprings. And more, we also use the prescription of regulating liver function to intervene maternal rats mentioned above, investigating the effects of drug intervention on the behaviors and neurobiochemistry of their adult offsprings. Striving to find the initial mechanism of abnormal emotions cause by liver failing and the possible function mechanism of the prescription of regulating liver function. Based on research findings, puting forward scientific hypotheses of "Different abnormal behavioral appearance in offsprings are attributed to maternal negative emotion stress before pregnancy , especially anger and depression"and providing theoretical guide and technical support to in-depth exploration of liver failing to convey and disperse pathogenesis and screening new drugs with definite effection targets.

我们及相关研究显示：母代肝疏泄失常对子代的行为有负性影响, 并且与子代高发的情感障碍类疾病有关。由肝失疏泄两证（肝气逆证、肝气郁证）典型的愤怒、抑郁情志异常入手，研究并揭示肝疏泄失常母代大鼠对子代大鼠行为和神经生化的影响，是探查肝失疏泄发生机制的关键科学问题。拟采用慢性温和刺激（CMS）及居住入侵（RIT）技术，诱发母鼠孕前肝疏泄失常证候表现，观察肝气疏泄太过及疏泄不及母鼠成年雄性子代行为及神经生化改变，运用中药调肝方药对上述母代大鼠进行干预，考察药物干预对其子代行为、神经生化指标的影响，争取发现肝失疏泄，情志异常的初步发生机制，以及调肝方药可能的作用机制。依据研究发现，提出"怫郁恚怒，情志所伤，邪伏于中，传及子代，表现各异"科学假说，为深入探索肝疏泄失常发病机制和筛选作用靶点明确的新药，提供理论向导和技术支撑。

本项目围绕肝疏泄失常母代大鼠对子代大鼠行为和神经生化的影响这一关键科学问题，按照原定计划开展了母鼠孕前肝疏泄失常模型的制备及评价；雄性子代大鼠行为学及神经生化检测；调肝方药药理效应可能作用机制探查步步深入研究。按照预期完成了全部研究计划，发表论文14篇，其中SCI收录1篇，中文核心13篇。获得“第三届情绪与健康和疾病及其中医药干预国际学术研讨会”暨“第七届中医基础理论分会学术年会”优秀论文1项。培养博士研究生1名、硕士研究生1名。首次探索社会挫败应激诱导孕前抑郁行为（肝疏泄不及状态）母鼠及居住入侵应激诱导孕前愤怒行为（肝疏泄太过状态）母鼠所产成年雄性子代的关键行为改变及可能神经生化机制，取得了重要研究进展和一系列有特色的创新性成果：建立母鼠孕前肝疏泄失常影响子代行为改变及其机制研究技术平台；提出母代接受的不同应激源会对子代造成不同的效应，肝气疏泄太过/不及母代会将上述行为异常表现传递给子代，使子代出现类似的肝气逆/郁“症状”，且有相应不同的底层机制；子代后天出现的肝气逆/郁证候表现是遗传/表观遗传与环境（包括发育环境和生活环境）因素共同作用后的演出型结果，是特定场景下的特定反应模式的理论新认识，为“怫郁恚怒，情志所伤，邪伏于中，传及子代，表现各异”假说提供科学证据。以上工作将为深入探索肝疏泄失常发病机制和筛选作用靶点明确的新药，提供理论向导和技术支撑。