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目的:探索灯盏乙素利用鼻腔嗅觉区的鼻-脑通道进行鼻脑靶向给药的可行性。方法:以注射给药为对照,于灯盏乙素鼻腔给药后一定时间用小脑延髓池穿刺术采集大鼠脑脊液,股动脉插管取血,125I标记法测定其在大鼠脑脊液、脑组织和血中药物含量,梯形法计算药物动力学参数;以AUCbrain/AUCplasma为指标评价脑靶向性。结果:大鼠鼻腔给药后灯盏乙素的脑内分布具有组织差异,经鼻腔吸收后5～15 min,嗅球即达峰值,在30～60 min时其在各脑组织中的药浓均达到峰值,其中,嗅球(574.8±205.9)ng.g-1、嗅区(323.4±128.3)ng.g-1、脑脊液(123.2±29.3)ng.g-1。灯盏乙素鼻腔给药后的脑部药浓分布如下:嗅球嗅区>脑脊液>小脑>延髓>大脑;相等剂量给药时,灯盏乙素鼻腔给药后嗅球、嗅区、CSF的AUC0～240分别为静注的5.54,5.07,5.51倍,其他脑组织的AUC0～240均大于静注。灯盏乙素鼻腔给药后各脑组织的AUCbrain/AUCplasma均显著高于静注给药,5 min时嗅球、CSF、大脑的AUCCR/AUCplasma值分别是静注的56.93,30.45,6.14倍。结论:灯盏乙素鼻腔给药后可能经以下吸收通路直接转运入脑:经鼻腔嗅黏膜吸收进入蛛膜下腔的嗅球,然后相继进入嗅区、CSF、大脑、小脑等部位,嗅球是药物分子经鼻腔入脑的必经之路。与静注给药相比,灯盏乙素鼻腔给药具有明显的脑靶向性。
Objective: To investigate the feasibility of Scutellaria B by nasal-brain channel of nasal olfactory area. Methods: The rats were injected intranasally with scutellarin for a period of time. Cerebrospinal fluid (CSF) was collected from the cerebellomedullary cistern and punctate into the femoral artery for catheterization. The levels of IL-6 in cerebrospinal fluid (CSF) and brain tissue Blood drug content, trapezoidal method to calculate pharmacokinetic parameters; AUCbrain / AUCplasma as an index to evaluate brain targeting. Results: The intracerebral distribution of scutellarin in rats after nasal administration had tissue differences. After 5 to 15 min of nasal absorption, the olfactory bulb peaked and reached its peak in all brain tissues at 30 to 60 min (574.8 ± 205.9) ng.g-1, olfactory region (323.4 ± 128.3) ng.g-1 and cerebrospinal fluid (123.2 ± 29.3) ng.g-1, respectively. The distribution of brain drug concentration after intranasal administration of scutellarin is as follows: olfactory bulb olfactory area> cerebrospinal fluid> cerebellum> medulla oblongata> brain; when the same dose is administered, the AUC0 ~ 240 of olfactory bulb, olfactory area and CSF after scutellarin administration Respectively 5.54,5.07,5.51 times the intravenous injection, other brain tissue AUC0 ~ 240 are greater than the intravenous injection. The AUCbrain / AUCplasma of each brain tissue after intranasal administration of scutellarin was significantly higher than that of intravenous injection. The AUCCR / AUCplasma values of olfactory bulb, cerebrum and cerebrum at 5 min were 56.93, 30.45 and 6.44 times of that of intravenous injection, respectively. CONCLUSIONS: Scutellarin may be directly transported into the brain via the following absorption pathways after intranasal administration: the nasal olfactory mucosa absorbs into the olfactory bulb of the subarachnoid space, and then successively enters the olfactory area, CSF, brain and cerebellum and other parts. The olfactory bulb is a drug molecule The only way through the nasal cavity into the brain. Compared with intravenous administration, scutellarin nasal administration has obvious brain targeting.