磁导向纳米磁性药物载体对迟发型脑血管痉挛干预的实验研究  

The interventional effect of magnetic nanoparticle-albumin-2,2'-dipyridyl( MNA-DPD) on delayed cerebral vasospasm

作　　者：汪子文[1] 桂铮 卢学刚[2] 郭栋[1] 朱明[1] 李臻[1] 韩新巍[1] 于耀宇[1] WANG Ziwen GUI Zheng LU Xuegang GUO Dong ZHU Ming LI Zhen HAN Xinwei YU Yaoyu(Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450001 Department of Material Physics, School of Science, Xi＇an Jiaotong University, Xi＇an 710049, China)

机构地区：[1]郑州大学第一附属医院介入科,河南郑州450001 [2]西安交通大学理学院材料物理系,陕西西安710049

出　　处：《中华神经外科疾病研究杂志》2017年第4期293-296,共4页Chinese Journal of Neurosurgical Disease Research

基　　金：国家自然科学基金资助项目(81171116)

摘　　要：目的探讨在磁导向下纳米磁性药物载体(MNA-DPD)对迟发型脑血管痉挛(DCVS)干预的有效性。方法健康成年新西兰白兔100只,随机分为5组:正常组(n=20),处理组(n=20):溶剂对照组(DMSO)、纳米磁性蛋白组(MNA)、2-2'联吡啶组(DPD)和纳米磁性药物载体组(MNADPD)。处理组采用二次注血法制作DCVS模型,然后每天分别通过腰大池给予0.01%DMSO、MNA、DPD和MNA-DPD,剂量50 mg/kg。MNA组、MNA-DPD组给予外加磁场磁导向。在给药7 d时处死动物,取其基底动脉行HE染色并测定管径,同时行普鲁士蓝染色。Western Blot定量分析给药后7 d动物模型基底动脉增殖细胞核抗原(PCNA)、血管内皮生长因子(VEGF)、c-Myc蛋白和p53蛋白表达水平。结果 HE染色和普鲁士蓝染色显示DMSO组、MNA组基底动脉明显痉挛,DPD组基底动脉可见痉挛,MNA-DPD组基底动脉基本正常的形态(P<0.05)。并可见蛛网膜下腔的纳米磁性微粒被染成蓝色。Western Blot定量分析PCNA、p53、c-Myc、VEGF蛋白在DMSO组、MNA组和DPD组呈现高表达,MNA-DPD组呈现低表达(P<0.05)。结论在磁导向下,腰大池给予纳米磁性药物载体,能够有效地抑制DCVS。Objective The interventional effect of magnetic nanoparticle-albumin-2, 2＇-dipyridyl （MNA-DPD） on delayed cerebral vasospasm （DCVS） with magnetic field targeting was explored. Methods The experimental animals, 100 healthy adult New Zealand rabbits, were randomly divided into 5 groups： dimethyl sulphoxide group （DMSO）, magnetic nanoparticle- albumin group （MNA）, 2, 2＇-dipyridyl group （DPD）, magnetic nanoparticle-albumin-2, 2＇-dipyridyl group （MNA-DPD）, and control group. DCVS models were made by the secondary injection of blood in DMSO group, MNA group, DPD group and MNA- DPD group. 0. 01% DMSO, MNA, DPD and MNA-DPD were administered respectively in each experimental group once every day （50 mg/kg）. Focusing magnetic field was guided in MNA group and MNA-DPD group. In 7 d after injection, animals were killed and given perfusion fixation. Basilar arteries were extracted for HE staining, Prussian blue staining and Western Blot test. The expression of proliferating cell nuclear antigen （PCNA）, vascular endothelial growth factor （VEGF）, c-Myc protein and Tumor protein p53 in the seventh day were measured with Western Blot test. Results At 7 d after injection, HE staining and Prussian blue staining showed obvious vasospasm in DMSO group and MNA group, moderate vasospasm in DPD group and nearly no vasospasm in MNA-DPD group. It was significantly different in MNA-DPD group compared with MNA group, DPD group and DMSO group （ P 〈 0. 05 ）. Prussian blue staining showed magnetic nanoparticles were dyed blue in the subarachnoid space of MNA group and MNA-DPD group. Western Blot test indicated high expression of PCNA, P53, c-Myc and VEGF in DMSO group, MNA group and DPD group, while low expression in MNA-DPD group （P 〈0. 05）. Conclusion MNA-DPD injection via lumbar cistern can effectively relieve DCVS in rabbits with magnetic field targeting.

关 键 词：磁导向纳米磁性药物载体 迟发性脑血管痉挛 蛛网膜下腔出血 

分 类 号：R743.35[医药卫生—神经病学与精神病学]