降钙素基因相关肽经鼻靶向中枢给药的实验研究

The experimental study of intranasal administration of calcitonin gene related peptide targeting in the central administration

目的寻找无创、直接有效的靶向中枢给药方法,将降钙素基因相关肽(CGRP)避开血脑屏障(BBB)直接运送到中枢神经系统。方法大鼠采取线栓法制作大脑中动脉闭塞模型(MCAO),在随机双盲状态下分组予以不同处理。利用酶联免疫吸附法(ELISA)测定经鼻腔和静脉注射CGRP后30min时,各脑区的CGRP浓度,研究CGRP经鼻给药的可行性。结果 IN组脑部各区域、颈髓和CSF中CGRP浓度较IV组显著增高(P<0.01),以嗅球的CGRP浓度最高,其次为CSF和颈髓。结论经鼻靶向中枢给药可以避开血脑屏障的阻碍,将CGRP递送至中枢神经系统,中枢神经系统的CGRP浓度显著提高。

Objective To develop a noninvasive method for delivering CGRP to the brain bypassing the blood- brain barrier （BBB） for the treatment of brain injury. Methods A blinded,vehicle-controlled study of IN CGRP and IV CGRP administration was performed by intraluminal middle cerebral artery occlusion （MCAO） model. The enzyme-linked immunosorbent assay （ ELISA ） was carried out after IN and IV injection of CGRP for 30min to measure CGRP concentration in different brain areas. The feasibility of intranasal administration CGRP were ana- lysed.Results CGRP demonstrated a much higher delivery of IN than IV CGRP to the brain regions. The olfactory bulb was the highest region followed by CSF and spinal cord. Conclusion CGRP might be delivered to the brain di- rectly from the nasal cavity following IN administration by passing the BBB.