重组人p53腺病毒基因经介入后在兔VX2肝癌中表达  

Expression of recombinant human adenovirus-p53 gene delivered into rabbit VX2 tumors by interventional methods

作　　者：罗仕华[1] 郑传胜[1] 冯敢生[1] 梁惠民[1] 周国锋[1] 夏向文[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院介入放射科,湖北省武汉市430022

出　　处：《世界华人消化杂志》2010年第5期437-442,共6页World Chinese Journal of Digestology

摘　　要：目的:探讨重组人p53腺病毒基因(rAd-p53,1×1012VP/支)经介入在兔VX2肝癌中的表达特点,为临床应用提供理论依据.方法:将30只新西兰大白兔采用移植法建立兔VX2移植性肝癌模型,于移植术11d行MRI、CT检查.随机抽取27只移植成功的荷瘤兔,平均分成3组:A组:经肝动脉单纯灌注rAd-p53(5×106VP);B组:rAd-p53(5×106VP)+超液态碘油(每只0.5mL)经肝动脉灌注;C组:瘤内rAd-p53(5×106VP)直接导入.所有荷瘤兔术中均行DSA.介入术后24、72h,6d分别处死实验兔,免疫组织化学方法检测肿瘤组织及瘤周P53和Bax、Bcl-2蛋白的表达.结果:30只大白兔均经MRI及CT检查,证实有27只种瘤成功,成功率95%.免疫组织化学检测各组中P53和Bax蛋白均有表达,于72h达到最高峰,以C组表达率最高,与其他两组有显著性差异(P53:70.3%±3.4%vs62.4%±3.2%,65.4%±2.1%;Bax:43.7%±2.1%vs35.7%±1.3%,37.6%±2.4%,均P<0.05);C组对Bcl-2蛋白表达率最低,在72h达最低点,与其他两组有显著性差异(12.0%±2.6%vs18.0%±4.3%,16.2%±3.1%,均P<0.05).结论:P53、Bax、Bcl-2蛋白在兔VX2肝癌模型中的表达呈现时间曲线关系;不同rAd-p53介入导入方式P53蛋白表达不同,以瘤内及瘤周直接注射方式表达最高,超液态碘油混合灌注及单纯肝动脉灌注次之.AIM：To investigate the expression of recombinant human adenovirus-p53 gene （rAd-p53,1× 10 12 VP） delivered into rabbit VX2 tumors by interventional methods.METHODS：Thirty New Zealand rabbits were used to establish an animal model of hepatocarcinoma by implantation of the VX2 tumors into the liver.Eleven days after implantation,magnetic resonance imaging （MRI） and computed tomography （CT） scans were performed.Successful implantation was achieved in 27 rabbits.These rabbits were randomly divided into three groups：A,B and C.Groups A and B were infused through the hepatic artery with rAd-p53 （5 × 10 6 VP） alone and rAd-p53 （5 × 10 6 VP） plus lipiodol ultra fluid （0.5 mL）,respectively,while group C was injected with rAd-p53 （5 × 10 6 VP） into tumors by surgery.All model rabbits underwent digital subtraction angiography （DSA） during operation.The expression of P53,Bax and Bcl-2 proteins in tumor and peritumoral tissue was detected by immunohistochemistry at 24 and 72 hours and on 6 days after the operation.RESULTS：MRI and CT scans showed that successful implantation was achieved in 27 rabbits,and the success rate was 95%.Immunohistochemical analysis indicated that P53,Bax and Bcl-2 proteins were expressed in all the three groups.The expression levels of P53 and Bax reached the peak at 72 hours.The expression levels of P53 and Bax in group C at 72 hours were significantly higher than those in groups A and B （P53：70.3% ± 3.4% vs 62.4% ± 3.2% and 65.4% ± 2.1%;Bax：43.7% ± 2.1% vs 35.7% ± 1.3% and 37.6% ± 2.4%,respectively;all P 0.05）.In contrast,the expression level of Bcl-2 in group C at 72 hours was significantly lower than those in groups A and B （12.0% ± 2.6% vs 18.0% ± 4.3% and 16.2% ± 3.1%,respectively;both P 0.05）.CONCLUSION：P53 protein is expressed in rabbit VX2 tumors in a time-dependent manner.The expression level of P53 protein depends on the delivery methods used.The highest expression of P53 protein is achieved by intratumoral injection,followe

关 键 词：兔VX2肿瘤 肝癌模型 重组人p53腺病毒基因 基因表达 

分 类 号：R735.7[医药卫生—肿瘤]