| 摘要: |
| 目的：自制纳米级超顺磁性氧化铁（superparamagnetic iron oxide,SPIO），观察其对小鼠的急性毒性作用，为进一步研究其长期毒性及将其作为载体应用于磁共振（magnetic resonance, MR）基因成像奠定基础。方法：采用共沉淀法制备纳米级SPIO，应用透射电镜、原子力显微镜及1.5 T超导型MR仪等测定其相关理化指标。90只小鼠按纳米级SPIO给药方式和剂量随机分为口服灌胃、静脉注射、腹腔注射组（n=30），分别按总剂量2 104.8 mg/kg、给药容积40 ml/kg口服灌胃；总剂量438.5 mg/kg、给药容积25 ml/kg静脉注射；以及总剂量1 578.6 mg/kg，给药容积30 ml/kg腹腔注射；各组另设10只小鼠按相应方式给予等量生理盐水作为对照（n=10）。给药后饲养14 d，观察饲养期间小鼠的一般情况，检测小鼠血清主要生化指标；观察主要脏器的病理学改变。结果：成功制备纳米级SPIO，其核心颗粒为Fe3O4 晶体，颗粒大小20～35 nm，T 2弛豫率0.155×106 mol-1·s-1，比饱和磁化强度68.395 68 emu/g，剩磁21.463 74 Gs。观察期间各组小鼠均未见死亡；各组小鼠血清生化指标无显著差异；HE染色及Wright骨髓染色见各组小鼠肝、脾、肾、心、肺和骨髓细胞均无水肿、变性、坏死等改变；普鲁士蓝染色见给药组小鼠肝、脾内分布少许铁蓝色颗粒，而对照组未见。结论：自制的纳米级SPIO符合作为MR成像对比剂的要求，对小鼠无明显急性毒性，值得进一步研究以用于磁共振基因成像。 |
| 关键词: 超顺磁性氧化铁 纳米技术 毒性试验 |
| DOI：10.3724/SP.J.1008.2007.01104 |
|
| 基金项目:重庆市卫生局医学科研项目（062025），重庆医科大学优秀博士基金（重医大文2006 182号）. |
|
| Preparation of superparamagnetic iron oxide nanoparticles and its acute toxicity to mice |
| WEN Ming1, SONG Lin2, BO Wei2, LI Shaolin2*, LI Bibo3 |
| (1.Department of Radiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China;2.Department of Radiological Medicine, the College of Basic Medicine, Chongqing Medical University;3.College of Pharmacology,Chongqing Medical University) |
| Abstract: |
| Objective：To prepare superparamagnetic iron oxide (SPIO) nanoparticles and to observe its acute toxicity on mice, so as to pave a way for further study on its longterm toxicity and on its role as a carrier in magnetic resonance gene imaging. Methods: The SPIO nanoparticle was obtained by means of coprecipitation, and its physical and chemical parameters were determined by transmission electron microscope, atomic force microscope, and 1.5 T super conduct MR, etc. According to the administration pathway and doses of SPIO, 90 mice were divided into oral administration (with a total dose of 2 104.8 mg/kg and a volume of 40 ml/kg, n=30), intravenous injection (a total dose of 438.5 mg/kg and a volume of 25 ml/kg, n=30) and intraperitoneal injection (with a total dose 1 578.6 mg/kg and a volume of 30 ml/kg, n=30) groups. Another 10 mice in each group receiving the same dose of normal saline via the same pathway served as the controls (n=10). The general condition, the major serologic parameters, and the pathological changes of major organs were observed 14 d after administration in each group. Results: We have successfully prepared SPIO, and its core component was Fe3O4 crystal, with a size of 2035 nm, a T2 relaxivity of 0.155×106 mol-1·sec-1, a specific saturated magnetization of 68.395 68 emu/g, and a retentivity of 21.463 74 Gs. There was no death of mice during the observation. There was no significant difference in serological parameters between mice of different groups and between each experiment group and their corresponding control group. No edema, degeneration and necrosis were seen in the liver, spleen, kidney, heart, and lungs by HE staining and marrow by Wright staining; only a few blue particles were observed in the liver and spleen in the administration groups by Prussian blue staining, none observed in the control groups. Conclusion: SPIO prepared in the present study meets the requirement of MR imaging, with no acute toxicity to mice, and warrants further study for future MR gene imaging. |
| Key words: superparamagnetic iron oxide nanotechnology toxicity tests |
