灯盏花素作用于嗅鞘细胞促神经血管单元构建的脑靶向机制研究

AIS is the third leading cause of death in the world today, and is also the leading cause of disability. A combination of both thrombolytic and neuroprotective is the ideal treatment of it. The injection of the main component breviscapine is the supreme frequency drug to treat AIS in clinical, and nasal delivery is an important route of administration for the brain targeting treatment of AIS. Studies show that nasal delivery breviscapine has better effect for AIS than intravenous administration, but its mechanism has not been studied in-depth. Acrid of chinese materia medica into the brain through the nose,dissipating stasia and dredging collaterals, which is the theoretical foundation of Chinese medicine of breviscapine brain targeting therapy for AIS; and olfactory ensheathing cells (OECs) are unique cells on nasal-brain pathway, with nutrition factors、adhesion factor and neurotrophoc factors of its secretion had very strong ability to promote cranial nerve regeneration. Therefore, this subject is to be used in vivo and in vitro research methods of rat, through studying the affect of Breviscapine on OECs proliferation, migration, the expression of migration relevant factors and neurotrophic factor, to discuss the overall effect of breviscapine nasal delivery enhancing the neurovascular unit constructed (NVU) after acting on OECs, and to elucidate the brain targeting mechanisms of promoting NVU constructed of breviscapine in OECs. Ultimately, to provide a scientific basis for neuroprotection to AIS of the nasal administration breviscapine, and to provide a experimental basis for the treatment of targeting effect to AIS.

AIS是当今世界第三大致死和首要致残的原因，其理想的治疗方案是溶栓和神经保护两者的结合。以灯盏花素为主要成分的注射液是临床治疗AIS使用频率最高的药物，而鼻腔给药是脑靶向治疗AIS的重要给药途径，研究表明灯盏花素鼻腔给药效果优于静脉给药，但其机制尚未进行深入研究。中药辛味入鼻通脑，散瘀通络，是灯盏花素脑靶向治疗AIS的中医药理论基础；而嗅鞘细胞（OECs）是鼻-脑通路上独特的细胞，其分泌的营养因子、粘附分子和促进神经生长因子具有很强的促进脑神经再生能力。因此本课题拟采用大鼠体内外研究方法，通过研究灯盏花素对OECs增殖、迁移、迁移相关因子表达及神经营养因子表达的影响，探讨灯盏花素鼻腔给药作用于OECs后促神经血管单元（NVU）整体构建的效果，以阐明灯盏花素作用于OECs促NVU构建的脑靶向机制，为灯盏花素鼻腔给药对AIS的神经保护提供科学依据，并为其治疗AIS的靶向效果提供实验基础。

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