中文摘要：

目的探讨纳米氧化铝颗粒对小鼠血脑屏障通透性的影响。方法 3月龄ICR小鼠用滴鼻法染毒,为了比较纳米铝作用的颗粒毒性和化学毒性,将小鼠分为对照组、微米铝组、纳米碳组、纳米铝组和铝离子组;为了比较纳米铝作用的剂量-效应关系,将小鼠分为对照组、低剂量组、中剂量组和高剂量组。每只小鼠每次染毒10μl,3次/d,实验时间为30 d。染毒结束后,用硝酸镧染色法检测血脑屏障通透性;用免疫荧光法检测紧密连接蛋白ZO-1、Occludin蛋白表达;用western blot法检测ZO-1,Claudin-5蛋白表达。结果硝酸镧染色结果表明,对照组的硝酸镧颗粒聚集在毛细血管中央,未见对血管内皮的穿透;微米铝组和纳米碳组有部分高电子密度的硝酸镧颗粒位于毛细血管内壁中央,显示血脑屏障的通透性增高;纳米铝和铝离子组有大量硝酸镧颗粒位于血管内壁中央,形成致密的黑色条带,显示血脑屏障受损和通透性增高。免疫荧光法检测紧密连接蛋白ZO-1、Occludin蛋白表达和western blot法检测ZO-1,Claudin-5蛋白表达结果表明,紧密连接蛋白ZO-1、Occludin和Claudin-5蛋白表达在对照组均为高表达,微米铝和纳米碳组表达下调（P〈0.0001）,纳米铝和铝离子组的表达量最低（P〈0.0001）。且这种紧密连接蛋白表达的降低与纳米铝的染毒剂量间有剂量-反应关系（P〈0.0001）。结论纳米氧化铝可以降低血脑屏障通透性,这种作用表现为纳米的颗粒作用和铝化学毒性作用的相加。其发生机制与紧密连接蛋白ZO-1、Occludin和Claudin-5蛋白表达降低有关。

英文摘要：

Objective To study the effect of nano-alumina （nano-Al） on the blood brain barrier （BBB） of mice. Methods Three-month old ICR mice were exposed to nano-alumina by nasal drip method. To compare the toxicity of nanoparticle and chemistry, the mice were divided into 5 groups, as control, micro-alumina （micro-Al） , nano-carbon （nano-C） , nano-Al and aluminum （Al） ion. To compare the dose effect of nano-Al, the mice were divided into 4 groups, as control, low-dose group, mid-dose group and high-dose group. Each mouse was poisoned 3 times/day, 10 p~L/time, the course lasted 30 days. Lanthanum nitrate dyeing was used to detect the permeability of BBB, immunofluorescent chemistry was used to determine protein levels of ZO-1 and Occludin, western blot was used to measure the protein levels of ZO-1 and Claudin-5. Results The results of Lanthanum nitrate dyeing demonstrated that the particles of lanthanum nitrate surrounded in the middle of capillaries, no permeability was observed; those of micro-Al and nano-C treated mice partly presented in the middle of capillaries, showing higher BBB permeability; while most of the lanthanum nitrate particles of nano-Al and AI ion treated mice located in the middle of capillaries, forming a dentist trip, displaying BBB injury and permeability rise. Protein levels of ZO-1, Claudin-5 and Occludin were highest in the control group, lower in the micro-Al and nano-C groups （P 〈 0. 0001 ） , and lowest in the nano-Al group （ P 〈 0.0001 ）. Furthermore, there was a dose-dependent relationship between the expression of doses and BBB permeability （ P 〈 0. 0001 ）. Conclusion Nano-Al could decrease the permeability of BBB, it derived from the combined toxicity of nanoparticle and chemistry. The mechanism may concern with the decreased proteins expression of ZO-1, Occludin and Claudin-5.