不同浓度载HSV1-TK基因的超声靶向微泡造影剂对HIFU治疗后裸鼠肝癌的影响  

Effects of Ultrasound-targeted Microbubbles Encapsulating HSV1-TK Gene in Nude Mice Hepatocellular Carcinoma after HIFU Treatment

作　　者：李红阳[1] 周世骥[1] 刘长安[1] 李生伟[1] 龚建平[1] 丁雄[1] 谭晶[2] 刘作金[1] 

机构地区：[1]重庆医科大学附属第二临床学院肝胆外科,重庆400010 [2]云南省肿瘤医院肝胆外科,昆明65000

出　　处：《中国医科大学学报》2013年第1期31-34,37,共5页Journal of China Medical University

基　　金：国家自然科学基金资助项目(30872977);重庆市卫生局科研项目(2012-1-040)

摘　　要：目的研究高强度聚焦超声(HIFU)治疗裸鼠肝癌后,观察不同浓度载HSV1-TK基因超声靶向微泡造影剂对裸鼠残留肝癌组织中TK基因表达的影响。方法建立裸鼠肝癌模型40只,随即分成4组,每组10只,使用JC200型HIFU治疗仪对裸鼠消融80%后,经裸鼠尾静脉注入不同浓度载基因微泡,然后用超声辐照,Real time PCR检测TK mRNA表达情况,免疫组化及Western blot检测TK蛋白的表达情况,绘制抑瘤曲线。结果免疫组化及Real time PCR及Western blot及抑瘤率均显示与A组相比,B、C、D组有统计学意义(P<0.05),而C、D组比较无统计学意义(P>0.05)。结论当携基因微泡浓度≤0.6μg/μL时,TK mRNA和蛋白的表达、抑瘤率与微泡呈浓度依赖,而当携基因微泡浓度>0.6μg/μL时,基因的表达及抑瘤率与微泡浓度无相关性,故携基因的微泡浓度为0.6μg/μL时TK基因表达最强。Objective To observe the effects of different concentrations of ultrasound targeted microbubbles loaded HSV1-TK gene expres- sion in nude mice hepatocellular carcinoma after HIFU treatment. Methods A total of 40 nude mice with hepatocellular carcinoma were randomized into 4 groups after HIFU, then ultrasound was applied at 1 MHz, 2 W/cm2, irradiation 5 min. TK gene expression was detected by RT-PCR, IHC and Western blot was used to detect the TK protein expression. Results The results of Western blot, PCR and immunohisto- chemical detection showed the TK gene expression of group B ,C,D was higher than group A （P 〈 0.05） ,there was no significant difference of TK gene expression between group C and group D （P 〉 0.05）. Conclusion When concentration of microbubbles loaded gene less than 0.6 μg/μL,the mRNA and protein expression of TK and the tumor inhibition rate was concentration dependent.When concentration of mi- crobubbles loaded gene more than 0.6 μg/μL,the gene expression has no correlation with the concentration of microbubbles. Therefore,the best concentration of microbubbles loaded gene is 0.6 μg/μL.

关 键 词：超声微泡 浓度 HSV1-TK 肝癌 

分 类 号：R73[医药卫生—肿瘤]