交变磁场下Fe3O4纳米磁流体对裸鼠移植性肝癌的杀伤作用

The effect of Fe3O4 nanometer magnetic fluid induced hyperthermia on implanted liver cancer in nude mice

目的研究交变磁场作用下Fe3O4。纳米磁流体对HepG2裸鼠移植性肝癌细胞的杀伤作用。方法建立HepG2裸鼠肝癌移植模型，将荷瘤裸鼠随机分成空白对照组、磁场空白组、Fe3O4纳米磁流体组3组。其中空白对照组不做任何处理；磁场空白组仅接受磁场作用不做其他处理；Fe304纳米磁流体组于裸鼠肿瘤部位直接注射PEG（polyethylene glyc01）-PEI（polyetherimide）／Fe3O4纳米磁流体后接受磁场作用。实验中，交变磁场发生频率为40kHz，磁场强度峰值为5kA／m，作用时间为15min／d，共15d，观察并记录7、15d两个时段皮下肿瘤体积、重量的变化情况，以及肿瘤的病理改变和肝癌细胞凋亡情况。结果裸鼠移植性肝癌肿瘤的成瘤率为100％，7和15d的记录显示Fe3O4纳米磁流体组裸鼠肿瘤体积和重量均小于其他两组，抑瘤率为54．20％（t=14．506，P〈0．01），明显高于磁场空白组的22．66％（t=7．497，P〈0．05）。空白对照组的肿瘤细胞生长良好，细胞密度大，核大深染，形态不规则，核分裂象多见；磁场空白组肿瘤细胞较为稀疏，间质增多，有坏死区形成；纳米磁流体组有大量的肿瘤细胞呈凝固性坏死，细胞核分解、消失，血管明显减少，肿瘤细胞分布稀疏。结论Fe304纳米磁流体在交变磁场的作用下，对HepG2裸鼠移植性肝癌细胞有显著的抑制作用。

Objective To study the therapeutic effect of Fe3O4 nanometer magnetic fluid-induced hyperthermia on implanted liver cancer in nude mice under alternating magnetic field. Methods Nude mice model bearing implanted HepG2 was established. Mice were then randomly divided into 3 groups： the blank control group; the magnetic field group; nanometer magnetic fluid group. The magnetic field group were just put under the magnetic field; Nanometer magnetic fluid group received injection of PEG-PEI/ Fe304 nanometer magnetic fluid under the alternating magnetic field. At the frequency of 40 kHz, and magnetic field of 5 kA/m, 15 minutes one day in the next 14 days. On the 7th day and the 15th day, the changes of tumor volume and weight were recorded, cell apoptosis were observed and recorded and pathological examination was done. Results On the 7th and the 15th day, in the nanometer magnetic fluid group, tumors＇ volume was smaller and the weight was lighter than other groups, and the tumor inhibitory rate of 54. 20% （t = 14. 506 ,P 〈 0. 01 ） was significantly higher than the control group and the magnetic field group 22. 66% （ t = 7. 497, P 〈 0.05 ）. In the control group, tumor cells grew well, high density, the nucleus engrained, the shape irregular, the nuclear fission clear; compared with the control group, in the magnetic field group, tumor cells scatter thinly, intercellular substance increases, and necrosis area formed; in the nanometer magnetic fluid group, many of tumor cells died, their cell nucleus broke up and vanished, the blood vessel reduced obviously, and the tumor cell spread thinly. Conclusions Under the alternating magnetic field, PEG-PEI/Fe3 04 nanometer magnetic fluid inhibits liver cancer growth in nude mice model of HepG2.