CGRP经鼻用药促进蛛网膜下腔出血后脑血供和VEGF表达  

Promotion of cerebral blood supply and expression of vascular endothelial growth factor by intranasal delivery of calcitonin gene-related peptide after subarachnoid hemorrhage

作　　者：孙保亮[1] 申发平[1,2] 曹明志[3] 杨明峰[1] 袁慧[1] 张颜波[1] 谢方民[4] 

机构地区：[1]山东省高校脑微循环重点实验室、泰山医学院附属医院神经内科,山东泰安271000 [2]大庆油田总医院集团龙南医院,黑龙江大庆163001 [3]济宁医学院附属湖西医院神经外科,山东菏泽274300 [4]泰山医学院附属医院神经外科,山东泰安271000

出　　处：《中国药理学通报》2009年第12期1571-1574,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30670724,30770759);山东省自然科学基金资助项目(NoY2007C014);山东省教育厅科技计划资助项目(NoJ05L10);山东省卫生系统高层次人才基金资助项目

摘　　要：目的探讨经鼻给予降钙素基因相关肽(CGRP)对蛛网膜下腔出血(SAH)后脑血供和血管内皮生长因子(VEGF)表达的影响。方法将Wistar大鼠随机分入正常对照组、SAH组、经鼻生理盐水(NS)+SAH、经鼻CGRP+SAH组。用枕大池两次注入自体动脉血法制作SAH模型,CGRP和NS经鼻腔给予。用激光多普勒血流计检测皮层局部脑血流量(rCBF)动态变化;于第2次枕大池注血后3d,将大鼠处死取脑制作冰冻切片,用免疫荧光结合激光共聚焦显微镜检测大脑皮层VEGF蛋白表达。结果解剖学观察表明SAH模型制作成功。SAH组和经鼻NS+SAH组大鼠大脑皮层rCBF持续下降,经鼻CGRP+SAH组大脑皮层rCBF下降的程度较轻。第2次枕大池注血后3d,SAH组和经鼻NS+SAH组大鼠大脑皮层VEGF蛋白表达增多,经鼻CGRP+SAH组大鼠大脑皮层VEGF蛋白表达进一步增强。结论CGRP经鼻用药可缓解SAH脑血供下降,并促进血管新生。Aim To investigate the influence of intranasal delivery of calcitonin gene-related peptide（CGRP）on cerebral blood supply and expression of vascular endothelial growth factor（VEGF）following experimental subarachnoid hemorrhage（SAH）.Methods Wistar rats were divided into normal control group,SAH group,intranasal normal saline（NS）＋SAH group and intranasal CGRP＋SAH group.SAH models were produced by double injection of autologous arterial blood into cisterna magna.CGRP and NS were given by intranasal perfusion.Dynamic observations of regional cerebral blood flow（rCBF）of cerebral cortex were made using a laser Doppler flowmeter probe.On the third day after the second cisternal injection,the expression of VEGF protein in cerebral cortex was observed by immunofluorescence method combined with laser confocal microscopic observation.Results Anatomic observation revealed that SAH models were successfully manufactured.In SAH and intranasal NS＋SAH groups,a drastic and persistent drop in rCBF was noted during the observed periods.The decrease of rCBF in intranasal CGRP＋SAH group was slighter as compared with that in SAH and intranasal NS＋SAH groups.In SAH and intranasal NS＋SAH groups,increased expression of VEGF protein in cerebral cortex was observed on the third day after second cisternal injection as compared with that in normal control group.The expression of VEGF in intranasal CGRP＋SAH group was more obvious than that in intranasal NS＋SAH group.Conclusion Intranasal delivery of CGRP improves cerebral blood supply and promotes angiogenesis by enhancing the expression of VEGF after SAH.

关 键 词：降钙素基因相关肽 经鼻给药 蛛网膜下腔出血 脑血管痉挛 脑血供 血管内皮生长因子 血管新生 

分 类 号：R-332[医药卫生] R322.81