电针干预慢性应激模型大鼠CREB-BDNF通路表观遗传学表达的机制研究

项目名称： 电针干预慢性应激模型大鼠CREB-BDNF通路表观遗传学表达的机制研究

项目编号： No.81202766

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 史榕荇

作者单位： 中日友好医院

项目金额： 24万元

中文摘要： 电针治疗抑郁症高效低毒副作用，是公认的绿色疗法。电针对抑郁症起整体调节作用，恢复机体固有动态平衡。抑郁症发病环境因素不容忽视，这与表观遗传学可随环境变化而变化的理论相吻合，弥补了经典遗传学理论不足。因此神经营养通路表观遗传学改变的系列研究成为揭示抑郁症发病机制的新热点，也是电针抗抑郁机制研究的新思路。电针激活CREB-BDNF通路增加BDNF表达提高神经可塑性，是通过激活CREB磷酸化，还是直接干预BDNF因子启动子，目前尚不明确。本研究以此为切入点，引入氟西汀对照组，CREB磷酸化拮抗组，采用放免法、Western-blot法、Real-time PCR法、甲基化PCR法，观察电针百会、印堂穴干预慢性应激模型大鼠CREB-BDNF通路相关因子蛋白、mRNA及表观遗传学表达改变，探讨电针抗抑郁机理。旨在从多层次、多角度揭示针刺抗抑郁途径，为针刺整体调节理论提供全新科学佐证，拓展学术空间。

中文关键词： 抑郁症；针刺；CREB-BDNF通路；BDNF因子；表观遗传学

英文摘要： Electroacupuncture (EA) is recognized as an effective rapid-acting antidepressant treatment without significant side effects and drug toxicity. EA can give the depressive body an holistic adjustment to bring it back to its normal dynamic balance. Therefore,how to clarify its mechanism, develop the advantages, and improve its positive effectiveness, has been becoming a valuable and urgent researching topic. The environmental factor is strongly associated with the occurrence of antidepressant. This is consistent with epigenetic expression can be changed with environment, which is considered as a supplementation of the field of traditonal genetics. So more and more researches focus on the epigenetic alteration on the CREB-BDNF signaling pathway on neural plasticity in the development of depression and disclosing the mechanisms of antidepressant.According to this theory, a new research derection of depression is also raised in EA treatment. EA can stimulate CREB-BDNF pathway, increase expression of BDNF factor, and enhance the capability of neural plasticity in depression. But where EA exerts its action on CREB-BDNF pathway, whether on increasing CREB phosphorylation or turnning the BDNF genes itself directly, is still unknown. Thus, we are going to launch a study from this fresh perspective in antidepressant treatm

英文关键词： depression；acupuncture；CREB-BDNF pathway；BDNF；epigenetics