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  

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

作　　者：王健君[1] 李艳茹[1] 李晓敏[1] 张海英[1] 王琳[1] 

机构地区：[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

出　　处：《吉林大学学报（医学版）》2008年第2期179-182,共4页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(30370547);教育部新世纪优秀人才支持计划资助课题(2004);教育部优秀青年教师资助计划项目(2003)

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。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-y 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-y 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-mlL-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.

关 键 词：水流动力学注射 白细胞介素12 基因疗法 腹水 

分 类 号：R-332[医药卫生] R730.5