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阿霉素纳米粒对颅内移植G422小鼠的化疗实验研究
作者:孙远召1 杨天明2 
单位:1.东南大学,临床医学院,江苏,南京,210009; 2.东南大学附属中大医院,神经外科,江苏,南京,210009
关键词:纳米粒 阿霉素 胶质母细胞瘤 化疗 
分类号:R739.41, R-33
出版年·卷·期(页码):2006·25·第五期(341-345)
摘要:

目的:观察阿霉素纳米粒对颅内移植G422胶质母细胞瘤小鼠化疗后的生存期变化及病理改变,评估阿霉素纳米粒对胶质母细胞瘤的化疗效果.方法:将G422胶质母细胞瘤细胞移植入86只昆明小鼠脑白质中建模,然后随机分为6组,分别是大剂量阿霉素纳米粒(3×2.5 mg·kg-1)、中剂量阿霉素纳米粒(3×1.5 mg·kg-1)、小剂量阿霉素纳米粒(3×1.0 mg·kg-1)、空白纳米粒(3 ×2.5 mg·kg-1)、阿霉素生理盐水(3×2.5 mg·kg-1)和不予任何治疗的控制组.移植后第2、5、8天由尾静脉给药.肿瘤移植后第10天进行流式细胞仪、组织病理学检查.结果:与同等剂量的阿霉素生理盐水组相比,大剂量阿霉素纳米粒组生存期显著延长.各个剂量的阿霉素纳米粒组化疗效果与剂量呈正相关.组织病理学检查证实大剂量阿霉素纳米粒组肿瘤体积最小,肿瘤边缘清楚,未发现肿瘤细胞浸润,而阿霉素生理盐水组的脑肿瘤边缘不清楚,肿瘤呈浸润性生长.结论:阿霉素纳米粒可以作为治疗人类胶质母细胞瘤潜在的化疗药物.

Objective To evaluate the therapeutic potential of doxorubicin-loaded nanoparticles in vivo using an animal model established by the implantation of G422 glioblastoma into mice brains.Methods G422 glioblastoma cells were implanted into white matters of mice.Mice having received implantation were randomized into 6 groups,which received varying doses of doxorubicin-loaded nanoparticles or doxorubicin in saline or blank treatment respectively.Doxorubicin were injected intravenously into their tail veins on days 2,5 and 8.Two mice were selected to receive either FCM or HE stain from the groups treated with 3×2.5 mg·kg^{-1} doxorubicin-loaded nanoparticles,doxorubicin in saline and blank treatment on day 10 respectively.Results Mice treated with doxorubicin-loaded nanoparticles in highest dose had significantly higher survival times compared with the group treated with doxorubicin in saline.The therapeutic effects of nanoparticles loaded with varying doses of doxorubicin were correlated with the dosages of doxorubicin loaded.Histologic pathological examination of brains confirmed that the nontreated mice developed tumors with the largest volume,while the mice treated with doxorubicin-loaded nanoparticle in highest dosage developed a minimal tumor size.The mice treated with doxorubicin in saline had diffusely invasive tumors,in contrast,mice treated with doxorubicin-loaded nanoparticle in highest dosage had solid tumors with clear margin.Conclusion The therapy of doxorubicin bound to nanoparticles offers a therapeutic potential for the treatment of human glioblastoma.

参考文献:

[1] 杨天明, 黄庆玖, 雍延平. 苯醋酸抗脑胶质瘤颅内移植实验研究. 南京铁道医学院学报1999(2)
[2] DAVID J. Delivery of therapeutic agents to the central nervous system:the problems and the possibilities. 2004(1). doi:10.1016/j.pharmthera.2004.08.001
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[6] 张炎, 鲁功成, 张润清. 阿霉素纳米粒的制备及体外逆转人膀胱癌细胞多药耐药的实验研究. 临床泌尿外科杂志2002(3). doi:10.3969/j.issn.1001-1420.2002.03.014
[7] SEBASTIAN C, KREUTER J, ALEXANDER S. Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles. 2004(5). doi:10.1002/ijc.20048 

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