降钙素基因相关肽经鼻给药进入中枢神经系统及促脑梗死修复的实验性研究

The experimental study of calcitonin gene- related peptide intranasal administration to central nervous system and prompt the repair of cerebral infarct

目的寻找快速、便捷有效的靶向中枢给药方法,为脑梗死治疗提供新的思路。方法线栓法制作大鼠大脑中动脉闭塞(Middle cerebral artery occlusion,MCAO)脑缺血再灌注模型,采用ELISA法测定经鼻(IN)和静脉(IV)注射CGRP后30 min时,各脑区的CGRP浓度,并观察IN和IV给予CGRP对局灶性脑梗死的治疗效果。结果IN给药组脑部各区域、颈髓和脑脊液(Cerebro-spinal fluid,CSF)中CGRP浓度较IV组显著增高(P<0.01),与IV组相比较,IN给药组梗死体积减小,脑血流量增加(P<0.01)。结论 CGRP经鼻靶向中枢给药可以避开血脑屏障阻碍,并对大鼠局灶性脑梗死有预防和保护作用。

Objective To develop a convenient and effective method for delivering CGRp to the central nervous system bypassing the blood-brain barrier（ BBB）,and to explore whether it had preventive and protective effects on cerebral in-farction in rats. Methods The MCAO model was made by nylon strand. CGRp concentration was measured IN and IV in-jection of CGRp after 30 min in different brain areas using enzyme-linked immunosorbent assay（ ELISA）,and explored the treatment IN and IV CGRp in rats with focal cerebral infarction. Results CGRp demonstrated a much higher delivery of IN than IV CGRp to the brain regions. Intranasal administration CGRp had significant preventive and protective effect to focal cerebral infarction which showed the brain infarction decreased and cerebral blood flow increased（ P〈0. 01 ）. Conclusion CGRp intranasal administration targeting central administration can avoid the blood-brain barrier block,and had preven-tive and protective effects on the rats with focal cerebral infarction. Intranasal administration CGRp had definite preventive and protective effect to focal cerebral infarction in rats.