纳米金颗粒对大鼠血脑屏障结构的影响

摘要

Objective To study the effect on the structure of blood-brain barrier after the intravenous administration of Au nanoparticles to the rats.Methods 50 nm Au nanoparticles were intravenous administra-ted into rats through jugular vein.CSF was then collected with a cauda equine catheterization technique at 1 , 2,3,4,5 and 6 hours respectively after the administration.And the concentration of Au was detected by ICP-MS analysis.After injection the nanoparticles of 6 hours,the brains of the rats were collected and stored as fixed films,and then to observe the nanoparticles and ultrastructure of brain tissue under the TEM.Other sam-ples were stained by Prussian blue dye,Immunohistochemistry and Immunofluorescence and observed bleeding and integrity of the blood-brain barrier under microscope after making slices of brain tissue in rats.Results The concentration of Au nanoparticles in CSF gradually increased and stabilized after 3 hours.Under TEM,a large amount of Au nanoparticles appeared in the brain tissue and there were some changes of the ultrastructure of the brain tissue.Under microscope,there were hemorrhages after blood-brain barrier in rats were stained by Prussian blue-positive dye and some brain blood vessels were damaged in the Immunofluorescence and Immuno-histochemistry staining slice.Conclusion Au nanoparticles are able to permeate the brain-blood barrier and cause micro bleedings and micro damages of brain vessel.%目的：观察颈静脉注射纳米金颗粒对大鼠血脑屏障结构的影响。方法经颈静脉向大鼠注射50 nm 金颗粒。分别在1、2、3、4、5、6 h 时收集大鼠脑脊液，采用电感偶合等离子体质谱仪检测脑脊液纳米金颗粒浓度。在注射纳米金颗粒6 h 后取脑组织并固定制片，在透射电镜下观察纳米金颗粒及脑组织的超微结构；大鼠脑组织制作切片后经普鲁士蓝染色、免疫组织化学染色和免疫荧光染色，在光镜下观察大鼠血脑屏障的出血情况和完整性。结果大鼠脑脊液中纳米金颗粒浓度随时间延长逐渐升高，并在3 h 后趋于稳定；电镜下可见大鼠脑细胞布满纳米金颗粒，超显微结构有一定改变；光镜下，大鼠血脑屏障在普鲁士蓝染色后可见出血点，在免疫组织化学染色和免疫荧光染色后可见血管缺损。结论纳米金颗粒可透过血脑屏障并造成微小出血点及血管微小缺损。