应用phfMRI研究苍艾挥发油的经鼻脑靶向作用和对抑郁症大鼠脑内单胺类神经递质通路的影响

经鼻脑靶向药物的研究是CNS药物研究的重要方向。因中药成分复杂、体内检测其代表性成分较难，使脑靶向性评价成为制约中药脑靶向药物研发的主要因素之一。利用phfMRI技术活体无创性评估药物对脑区功能活动的影响逐渐受到关注。前期研究发现苍艾挥发油（VOCA）经鼻给药，可显著提高大鼠脑功能活动水平，提示VOCA鼻腔给药存在鼻-脑通路，但其脑靶向性尚待研究。同时，VOCA能提高嗅球损毁大鼠抑郁相关脑区静态脑功能活动水平，增加脑内单胺递质的含量，因此推测VOCA具潜在抗抑郁活性。本课题拟利用phfMRI技术，按照生物效应法评价药物的脑靶向性，初步建立该技术评估中药挥发油鼻腔给药脑靶向性的方法。此外，拟复制大鼠慢性应激抑郁模型，采用基于种子区的相关分析法分析VOCA对不同单胺类神经递质通路之间相关度的影响，并用递质含量和通路相关蛋白表达加以验证，试从整体、器官和分子水平探讨VOCA治疗抑郁症的可能机制。

The study of targeted medicine through the nose-to-brain route is one of the main research directions for central nervous system (CNS) medicines. The complex composition of Chinese medicines and the difficulties of detecting the representative components in vivo makes evaluating the brain targeting of Chinese medicines difficult and constrains the research and development of this therapy. The application of pharmacological functional magnetic resonance imaging (phfMRI) has drawn increasing attention due to its ability for noninvasively evaluating the effects of medicines on the living encephalic regional functions. Previous studies have found that intranasal administration of volatile oil of Cang Ai (VOCA) can significantly improve the activity level of cerebral functions in rats, which suggests that VOCA via intranasal administration has a nose-to-brain route. However, the brain targeting of VOCA requires further study. Moreover, VOCA can improve the activity level of depression related encephalic regional static functions and increase the content of encephalic monoamine neurotransmitters in rats with damaged olfactorius bulb. Therefore, VOCA may have an antidepressant effect. This project will evaluate the brain targeting of VOCA using the technique of phfMRI according to the biological effects method and also establish a preliminary brain-targeting evaluation method for Chinese medicine volatile oil using phfMRI. Furthermore, this project will adopt the chronic stress-induced depression rat model and seed-based correlation analysis method to analyze the effect of VOCA on the degree of correlation among different monoamine neurotransmitter pathways. The neurotransmitter contents and pathways related protein expression will also be tested.The possible mechanism of VOCA’s anti-depressant effect will be investigated at the asholistic level， organ level and molecular level.