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• 基础医学 • 上一篇    下一篇

水流动力学注射介导的IL-12基因对小鼠恶性腹水的治疗作用

王健君,李艳茹,李晓敏,张海英,王 琳   

  1. 吉林大学基础医学院 病理生物学教育部重点实验室, 吉林 长春130021
  • 收稿日期:2007-05-09 修回日期:1900-01-01 出版日期:2008-03-28 发布日期:2008-03-28
  • 通讯作者: 王 琳

Hydrodynamic injection-mediated IL-12 gene therapyin mouse model of malignant ascites

WANG Jian-jun,LI Yan-ru,LI Xiao-min,ZHANG Hai-ying,WANG Lin   

  1. Key Laboratory of Pathobiology,Ministry of Education,School of Basic Medical Sciences,Jilin University,Changchun 130021,China
  • Received:2007-05-09 Revised:1900-01-01 Online:2008-03-28 Published:2008-03-28
  • Contact: WANG Lin

摘要: 目的:应用水流动力学注射基因转移法转移白细胞介素12(IL-12)基因,观察其对小鼠恶性腹水的治疗效果。方法:通过小鼠腹腔注射H22肿瘤细胞建立恶性腹水模型。将小鼠分为3组,接种后第3天通过水流动力学注射方法分别注射质粒pCMV-mIL-12、pCMVβ和生理盐水(NaCl)进行治疗。治疗后一定时间点取血检测血清中IL-12、干扰素-γ(IFN-γ)和一氧化氮(NO)的含量。注射后第14天各组分别处死3只小鼠,测量腹水体积,腹水细胞进行HE和AO/EB染色。其余小鼠用于观察生存期。结果:与只注射pCMVβ或生理盐水的小鼠相比,接受pCMV-mIL-12治疗的小鼠的生存时间明显延长(P<0.01),而且小鼠血清中IL-12、IFN-γ和NO水平明显升高(P<0.01或P<0.05),小鼠腹水中有活力的肿瘤细胞明显减少(P<0.01),凋亡的细胞增多(P<0.01)。结论:水流动力学注射介导的IL-12基因表达减少了恶性腹水小鼠的血性腹水生成并诱导肿瘤细胞凋亡,从而延长了小鼠生存期。

关键词: 白细胞介素12, 基因疗法, 腹水

Abstract: Objective To evaluate the antitumor efficiency of IL-12 gene mediated by hydrodynamic injection in mouse models of malignant ascites.Methods To prepare the malignant ascites model,H22 hepatoma cells were injected into peritoneal cavity of mice.The mice were divided into 3 groups.Plasmid pCMV-mIL-12,pCMVβ and saline were respectively administered into mice by hydrodynamic injection 3 d after H22 cells injection.Thereafter,the blood was collected at indicated time points.The expressions of IL-12 and IFN-γ and NO in serum were determined.Three mice were sacrificed 14 d after treatment.The volume of ascites was measured.The cells in ascites were stained with hematoxylin and eosin or AO/EB.The other mice were kept to monitor the survival.Results Compared with mice treated with pCMVβ or saline,the survival of mice treated with pCMV-mIL-12 was obviously prolonged (P<0.01).The significant elevation of IL-12 and IFN-γ and NO levels in serum were detected(P<0.01,P<0.05) and less alive tumor cells(P<0.01),more apoptotic cells (P<0.01) were observed in mice treated with pCMV-mIL-12. Conclusion Hydrodynamic injection-mediated IL-12 gene transfer can prolong the survival of mice bearing malignant ascites by decreasing the production of hemorrhagic ascites and inducing apoptosis of tumor cells.

Key words: interleukin-12, gene therapy, ascites

中图分类号: 

  • R-332