实用肝脏病杂志 ›› 2020, Vol. 23 ›› Issue (6): 777-780.doi: 10.3969/j.issn.1672-5069.2020.06.005

• 实验性肝炎 • 上一篇    下一篇

极低频率电磁场下Fe3O4纳米磁流体对小鼠种植性肝癌杀伤作用研究

谢环宇, 宫金伟, 赵明星, 孙继勇   

  1. 157000 黑龙江省牡丹江市 牡丹江医学院(谢环宇);
    黑龙江省绥化市第一医院普外一科(宫金伟,赵明星,孙继勇)
  • 收稿日期:2020-01-07 发布日期:2021-02-25
  • 通讯作者: 孙继勇,E-mail:gongjinwei321@163.com
  • 作者简介:谢环宇,男,26岁,硕士研究生,住院医师。主要从事肝脏疾病的诊断与治疗学研究。E-mail:zengdehui1980@sohu.com

Inhibitoryeffects of Fe3O4 nanometer magnetic carrier-induced hyperthermia under extremely low frequency electromagnetic fields on implanted tumors in nude mice

Xie huanyu, Gong Jinwei, Zhao MingXing, et al   

  1. Mudanjiang Medical College, Mudanjiang 157000,Heilongjiang Province, China
  • Received:2020-01-07 Published:2021-02-25

摘要: 目的 探讨在极低频率电磁场(ELF-EMF)下Fe3O4纳米磁流体对小鼠种植性肝癌的杀伤作用。方法 建立Bel-7402肝癌细胞裸鼠种植肿瘤模型,然后将荷瘤裸鼠随机分成对照组、磁场组和纳米磁流体组,每组20只。在对照组不行任何处理,在磁场组仅接受磁场作用下处理,在纳米磁流体组,给予裸鼠瘤内直接注射PEG-PEI/Fe3O4纳米磁流体0.1 ml,并接受0.7 mT的磁场下干预1 h,2次/d,作用15 d。采用放射免疫法检测血清血管内皮生长因子(VEGF)、缺氧诱导因子1α(HIF-1α)、白细胞介素 2受体(sIL-2R)和基质金属蛋白酶-2(MMP-2)水平。结果 在处理后7 d和15 d,纳米磁流体处理组裸鼠肿瘤体积分别为(113.5±12.2)mm3和(97.6±9.7)mm3],显著小于对照组 [(204.6±13.5)mm3和(452.8±16.5)mm3或磁场组(146.7±13.4)mm3和(118.8±13.6)mm3,P<0.05];对照组、磁场组和纳米磁流体处理组裸鼠肿瘤质量分别为[(2.0±0.2) g、(1.4±0.1)g和(0.8±0.1) g ,P<0.05],差异显著,磁场组和纳米磁流体组抑瘤率分别为26.2%和56.9%(P<0.05);纳米磁流体组血清VEGF、HIF-1α、sIL-2R和MMP-2水平分别为[(127.4±14.2)pg/ml、(32.4±5.2)ng/L、(227.5±23.7)ng/L和(132.4±15.7)pg/ml,显著低于对照组[分别为(294.6±18.6)pg/ml、(107.5±12.7)ng/L、(823.6±38.7)ng/L和(453.6±25.4)pg/ml,P<0.05]或者磁场组[分别为(215.7±14.3)pg/ml、(72.4±7.5)ng/L、(426.3±24.4)ng/L和(214.3.±18.4)pg/ml,P<0.05];对照组肿瘤细胞生长旺盛,细胞密度极大,排列紊乱,磁场组细胞生长受限,细胞排列稀疏,纳米磁流体干预组肿瘤组织呈大片坏死,肿瘤细胞显著减少。结论 在ELF-EMF下Fe3O4纳米磁流体对裸鼠种植性肝癌细胞血管生成有着显著的抑制作用,可显著抑制肿瘤生长,促进肝癌细胞凋亡。

关键词: Bel-7402肝癌细胞, 极低频率电磁场, 纳米磁流体, 裸鼠

Abstract: Objective The purpose of this experiment was to explore inhibitory effects of Fe3O4 nanometer magnetic carrier-induced hyperthermia under extremely low frequency electromagnetic fields (ELF-EMF) on implanted tumors in nude mice Methods A tumor model in nude mouse was established by implanted Bel-7402 liver cancer cells and the tumor-bearing nude mice were randomly divide into control, intervened in magnetic field and intervened in nano magnetic fluid under extremely low frequency electromagnetic fields (ELF-EMF), with 20 mice in each. The animals in experiment received intratumor injection of PEG-PEI / Fe3O4 0.1 ml under 0.7 mT magnetic field for 1 hour, twice a day and continued for 15 days. Serum VEGF, HIF-1α, sIL-2R and MMP-2 levels were detected. Results At day seven and fifteen, the tumor volume in nude mice in nano-magnetic fluid-treated group were (113.5±12.2) mm3 and (97.6±9.7) mm3, significantly smaller than in control group or in magnetic field-treated group [(204.6±13.5) mm3 and (452.8±16.5) mm3, or (146.7±13.4) mm3 and (118.8±13.6) mm3, respectively, P < 0.05]; the tumor weight was (0.8±0.1) g, significantly lower than [(2.0±0.2) g or (1.4±0.1) g, P <0.05] in control or in magnetic field-treated group, and the tumor inhibition rates in magnetic field and nanomagnetic fluid group were 26.2% and 56.9%, respectively (P < 0.05); serum VEGF, HIF-1α, sIL-2R, and MMP-2 were (127.4±14.2)pg/ml,(32.4±5.2)ng/L,(227.5±23.7)ng/L and (132.4±15.7)pg/ml], all significantly lower [(294.6±18.6)pg/ml,(107.5±12.7)ng/L,(823.6±38.7)ng/L and (453.6±25.4)pg/ml,respectively, P <0.05] in control or [(215.7±14.3)pg/ml,(72.4.±7.5)ng/L,(426.3±24.4)ng/L and (214.3.±18.4)pg/ml,respectively, P <0.05] in magnetic field; the histopathological examination showed the tumor cells in the control group grew vigorously, with large dense cells and disordered arrangement, the tumor cell growth in the magnetic field was restricted, sparsely arranged, with increased interstitial tissues, and the tumor in the nano-magnetic fluid group showed wide necrosis, with reduced tumor cells. Conclusion Fe3O4 nano-magnetic fluid intervention under ELF-EMF has a good inhibition effects on angiogenesis in implanted tumor in nude mouse, which could inhibit tumor growth and liver cancer cell proliferation, and promote apoptosis of the liver cancer cells.

Key words: Hepatoma cell lines, Extremely low frequency electromagnetic fields, Nano-magnetic fluid, Nuke mice