超声介导微泡造影剂促进HSV-TK基因转染抑制小鼠肝癌移植瘤的实验研究  

Murine Transplanted Hepatocarcinoma Treated with HSV-TK Plasmid Delivered by Microbubble Ultrasound Exposure:Experimental Study

作　　者：聂芳[1] 徐辉雄[2] 吕明德[3] 王瑛[2] 汤庆[2] 

机构地区：[1]兰州大学第二医院超声科,兰州市730030 [2]中山大学附属第一医院超声科,广州市 [3]中山大学附属第一医院肝胆外科,广州市

出　　处：《中国超声医学杂志》2008年第5期399-402,共4页Chinese Journal of Ultrasound in Medicine

基　　金：国家自然科学基金(No.3047046730300082);广东省科委重点攻关项目(No.2002C31108);广东省自然科学基金(No.04009360)

摘　　要：目的探讨超声辐照微泡造影剂介导的单纯疱疹病毒-胸苷激酶(HSV-TK)自杀基因系统转染小鼠肝癌组织的有效性。方法小鼠肝癌皮下移植瘤,尾静脉注入HSV-TK,添加或不添加SonoVue,脉冲多普勒超声(1MHz、2W/cm2、5min)辐照,第2天重复治疗1次。24h后荷瘤鼠腹腔注射更昔洛韦(GCV),连续10d,绘制肿瘤生长曲线,观测荷瘤鼠生存时间,半定量RT-PCR分析肿瘤内TK mRNA的表达,TUNEL染色检测肿瘤细胞凋亡。结果与单纯超声辐照组比较,超声(US)和SonoVue组肿瘤生长受到明显抑制(P<0.05),小鼠的平均生存时间延长(P<0.05),肿瘤内TK mRNA的表达增多(P<0.05),肿瘤细胞凋亡指数增高(P<0.05)。结论超声辐照SonoVue可有效介导HSV-TK基因发挥抗瘤效应。Objective To evaluate the efficiency of herpes simplex virus thymidine kinase （HSV-TK） suicide gene therapy in murine transplanted hepatocarcinoma mediated by microbubble ultrasound exposure. Methods Fourty mice bearing hepatocarcinoma subcutaneously were divided randomLy into 4 groups, plasmid HSV- TK was injected into tail vein with or without SonoVue. Pulse Doppler ultrasound was applied at a 1 MHz frequency with a 50% duty cycle and 2 W/cm^2 output intensity for 5 min, and the treatment was repeated the next day. In the following 10 d, ganclclovir （GCV） was given intraperitoneally on each day. The survival time of tumor-bearing mice was observed. Expression of TK mRNA was detected by RT-PCR, and transferase-mediated dUTP nick end labeling （TUNEL） staining was used to detect apoptotic cells. Results Compared with the group mediated by ultrasound alone, HSV-TK gene treatment mediated by ultrasound combined with SonoVue for restraining tumor growth and increasing survival time of tumor-bearing mice. TK mRNA expression and apoptotic index （AI） of the tumor exposed to ultrasound was increased after the addition of SonoVue （P〈0.05） .Conclusions Microbubble contrast agent SonoVue with ultrasound mediated HSV-TK shows marked inhibitory effect on murine transplanted hepatocarcinoma.

关 键 词：微泡造影剂 超声 基因治疗 肝肿瘤 

分 类 号：R735.7[医药卫生—肿瘤]