纳米氧化铜对豚鼠血脑屏障通透性影响观察  

Effect of copper oxide nanoparticles(CuONPs) on the permeability of guinea pigs blood-brain barrier(BBB)

作　　者：赵康峰[1] 候智全 张丽霞[1] 戴洪兴[2] 张少平[1] 张明[1] 李毅民[1] 白雪涛[1] 

机构地区：[1]中国疾病预防控制中心环境与健康相关产品安全所环境毒理室,北京100021 [2]北京工业大学环境与能源工程学院

出　　处：《毒理学杂志》2017年第5期340-344,共5页Journal of Toxicology

基　　金：国家自然科学基金(81372949)

摘　　要：目的观察40和200 nm 2种粒径纳米氧化铜颗粒(Cu ONPs)对豚鼠血脑屏障通透性造成的影响。方法制备粒径为40和200 nm的近球型Cu ONPs用于测试。以0.5%HPMC作为分散剂配制Cu ONPs染毒分散悬液。选取250~300 g的豚鼠用于试验。试验设40和200 nm Cu ONPs组、Cu SO4组、0.5%HPMC组和生理盐水组,每组5只动物。以一次性舌下静脉注射方式染毒。Cu ONPs组、Cu SO4组、HPMC组和生理盐水组染毒剂量分别按照1.5、65、4和4 ml/kg·bw进行。分别于染毒后24和48 h从每组取5只动物,先经舌下静脉给动物注射2%伊文氏蓝(EB)生理盐水溶液(4 ml/kg),1 h后实施心脏灌注,切取大脑顶叶皮质及皮质下结构组织,以脑组织中EB渗入量(以吸光度A值计)表示动物血脑屏障的开放程度。结果 40 nm Cu ONP作用24和48 h时皮质和皮质下结构组织A值明显高于相应200 nm Cu ONP组和生理盐水组A值差异有统计学意义(P<0.05)。2种粒径Cu ONPs组作用48 h的A值较各自作用24 h的A值明显增大差异有统计学意义(P<0.05)。同时,200 nm Cu ONPs组48 h皮质A值(0.383±0.017 A/mg)与生理盐水组A值(0.103±0.021 A/mg)之间差异有统计学意义(P<0.05)。除Cu SO4组24和48 h皮质下结构A值分别为0.087±0.026和0.071±0.031 A/mg高于对应生理盐水组,分别为0.041±0.013和0.069±0.022 A/mg外,其余各组的A值与生理盐水组间差异均无统计学意义(P>0.05)。结论 40 nm Cu ONP具有显著的致豚鼠血脑屏障开放效应,且这种效应在作用24~48 h具有增强特点。Objective To observe the effect of copper oxide nanoparticles （CuONPs） on the permeability of Guinea Pigs blood- brain barrier（BBB）. Methods Both 40 and 200 nm sized CuONPs with a globoid shape were synthesized to used in the study, and CuONPs was dispersed in 0.5% hydroxypropyl methylcellulose （HPMC） for convenient contamination. Guinea pigs with body-weighted 250 - 300 g were used in the study. Animals were randomly divided into 40 nm CuONPs, 200 nm CuONPs, CuSO4, HPMC and normal saline （NS） groups, 5 animals per group. The above groups were given with40 nm CuONPs, 200 nm CuONPs, CuSO4 , HPMC and NS with the dosages of 1.5 mg/kg.bw, 65 mg/kg-bw, 4 ml/kg, bw and 4 ml/kg, bw, respectively through sublingual venous injection route. 24 and 48 h after the initial exposure, animals were executed cardiac perfusion with NS after an injection of 2% evens blue（EB） （as 4 ml/kg.bw） respectively. Specimens of cerebral parietal cortex and subcortical structures were sampled. And the magnitude of permeability of BBB was quantitatively denoted by optical density （A） value of EB per mg of brain tissue （A/mg）. Result A values of 40 nm CuONP at 24 and 48 h in both cerebral parietal cortex and subcortical structures were statistically higher than the 200 nm CuONP group and the NS group correspondingly （P 〈 0. 05）. The 48 h valves of both 40 and 200 nm CuONP groups were greater than the 24 h values respectively. A value of 200 nm CuONP cerebral parietal cortex at 48 h was obviously higher than the corresponding NS groups value （ P 〈 0. 05） , which were respectively 0. 383 ±0. 017 A/mg and 0. 103 ±0. 021 A/mg. Except the CuSO4 group A values of subcortical structures at 24 and 48 h （0. 041 ±0. 013 and 0. 069 ±0. 022 A/mg respectively）were higher than the corresponding NS groups（0. 041 ±0. 013 and 0. 069 ±0. 022 A/mgrespectively） , no statistical difference between other test groups and the corresponding NS groups was found. Conclusion CuONPs can make the BBB open and whereby

关 键 词：氧化铜纳米颗粒 血脑屏障 通透性 影响 

分 类 号：R114[医药卫生—卫生毒理学]