超微超顺磁性氧化铁的制备及其对家兔毒性作用的研究

Preparation on Ultrasmall Superparamagnetic Iron Oxide Nanoparticles and Study of Its Toxicity to Rabbits

目的：制备超微超顺磁性氧化铁（USPIO），观察其对家兔的毒性作用，并研究其物理、磁学性质，探讨其作为磁共振阴性对比剂的可能性。方法：采用化学共沉淀法制备四氧化三铁（Fe3O4）纳米粒，采用X射线粉末衍射仪、透射电镜、磁强计及1．5T超导型磁共振仪等测定其相关理化指标。选取家兔20只，随机分为实验组（10只）和对照组（10只），实验组按1．25ml／kg耳缘静脉注射样品、对照组按1．25ml／kg耳缘静脉给予生理盐水。给药后于饲养2周末，检测其血清主要生化指标、观察主要脏器的病理学改变。并行MR检查观察实验组肝、脾的增强效果。结果：成功制备USPIO，核心粒径小于10nm，饱和磁化强度为47．2emu／g。给药后饲养2周，家兔无死亡。给药2周末予MR检查，实验组肝、脾在T2WI信号降低，对照组肝、脾在T2WI信号未见降低；两组家兔各项血清生化指标比较，差异均无统计学意义（P〉0．05）；其肝、脾组织进行普鲁士蓝染色，实验组家兔肝、脾内分布少许铁蓝色颗粒，而对照组均无铁蓝色颗粒。结论：采用化学共沉淀法制备的USPIO符合作为磁共振成像阴性对比剂的要求，通过给药家兔血清学、病理组织学及磁共振成像检查，说明USPIO生物相容性较好且毒性低，可作为磁共振的阴性对比剂用于肝、脾等部位磁共振成像。

Objective：To prepare uhrasmall superpara magnetic iron oxide nanoparticles and to observe its toxicity and physical and magnetic properties on rabbits, so as to explore its possibility for using as negative contrast agents in magnetic resonance imaging. Methods：The iron oxide nanoparticles was obtained by means of co precipitation method, and its physical and chemical parameters were determined by X ray diffraction, transmission electron microscopy, vibrating sample magnetometer and 1.5 T super conduct MR. 20 rabbits were randomly divided into experimental group （10） and the control group （10）. Experimental group was administration by intravenous injection with 1.25 ml/kg, control group receiving the same dose of normal salinevia the same pathway served. The major serologic parameters and the pathological changes of major organs were ob served two weeks after administration. The enhancing effect of liver and spleen, after injecting sample in was observed by MR. Results：USPIO was successfully prepared. The diameter of USPIO was less than 10 nm, and saturation magnetic intensity was 47.2 emu/g. Two weeks after administration, there was no death of rabbits, and inspect it with MR, the signal of T2WI MR images of liver and spleen decreased on experimental group, the signal of T2WI MR images of liver and spleen was not decreased on control group. There was no significant difference in serological parameters between experimental group and control group, their difference was not sta tistically significant（P 〉 0.05 ）. Liver and spleen were prussian blue staining. A few blue particles were ob served in the liver and spleen in the experiment group, none was observed in the control group. Conclusions： USPIO was prepared by co precipitation method consistent with negative magnetic resonance contrast medium,through administration rabbit serologic examination, histopathologic examination and nuclear magnetic reso- nance, and illustrate its biocompatibility is good and toxicity is low. It can be taken as negative magnetic reso- nance contrast medium are used for nuclear magnetic resonance of liver and spleen diseases diagnosis as nega- tive magnetic resonance constrast medium.