兔肝VX2肝癌经肝动脉化疗栓塞后碘油沉积及血管变化的研究  

The change of lipiodol retention and neovascularization in rabbits bearing VX2 liver tumor aftertranscatheter arterial chemoembolization

作　　者：林继宗[1] 王晨虎[2] 陈署贤[1] 林楠[1] 胡昆鹏[1] 方和平[1] 许瑞云[1] 

机构地区：[1]中山大学附属第三医院肝胆外科,广州510630 [2]无锡市第四人民医院肿瘤外科

出　　处：《中华实验外科杂志》2014年第4期753-756,共4页Chinese Journal of Experimental Surgery

基　　金：教育部博士点基金新教师类资助项目（20110171120090）;广东省科技计划资助项目（2011B061200005）

摘　　要：目的观察兔肝VX2肝癌经肝动脉化疗栓塞（TACE）术后碘油沉积及血管变化，为确定TACE术后联合射频消融（RFA）治疗最佳时间提供实验基础。方法采用“开腹瘤块包埋法”建立兔肝VX2肝癌模型，成模后行TACE术。将TACE术后肿瘤血管完全闭塞的30只兔肝癌模型根据观察时间点的不同，分为TACE术后24、48h，第7、14、21、28天共6组，通过影像学检查（CT扫描及动脉造影）和病理切片染色法观察各组肿瘤碘油沉积及微血管的变化。结果TACE术后24～48h肿瘤内碘油沉积完全，瘤周正常肝组织亦可见较多碘油沉积；7d后瘤周肝组织内碘油沉积减少，28d后肿瘤内碘油沉积不全；24h～21d肝动脉造影均未见肿瘤染色，28d后肿瘤局部可见云雾状染色。TACE术后21d肿瘤包膜内及肿瘤间质内有少量散在的小血管，28d肿瘤包膜内及肿瘤问质可见较多小血管。术后各组血管内皮生长因子（VEGF）阳性率逐渐升高，各组VEGF阳性率分别为（24．0±7．8）％、（27．0±9．1）％、（36．24±8．4）％、（53．0±9．5）％、（72．4±7．3）％、（73．6±12．1）％，术后48h、7、14、21d各组VEGF阳性率比较差异均有统计学意义（P〈0．05），而21d与28d比较差异无统计学意义（P〉0．05）。术后各组微血管密度（MVD）分别为10．8±5．3、12．0±6．0、12．6±3．8、24．3±5．4、38．8±9．5、39．6±6．2，术后第7天开始MVD呈上升趋势，7、14、21d各组MVD比较差异均有统计学意义（P〈0．05），而21d与28d比较差异无统计学意义（P〉0．05）。结论TACE术后48h内碘油沉积覆盖范围最广，血管闭塞最完全；7d后肿瘤组织VEGF表达上调，并随时间延长逐渐升高，在术后21d达到高峰；TACE术后7～14d肿瘤组织内微血管开始形成，21d有小血管出现，28d血管形成明显。Objective To observe the change of lipiodol retention and neovascularization in rab bits bearing VX2 liver tumor after transcatheter arterial chemoembolization （TACE）. Methods The mod els bearingVX2 liver tumor in 30 rabbits were randomly divided into group A （24 h） , B （48 h）, C （7 days ）, D （14 days）, and E （28 days） after TACE. Imageologic examinations, including CT scan and an giography, were done to observe the lipiodol retention and neovessels. HE staining and immunohistochemis try staining for vascular endothelial growth factor （VEGF） and CD34 were used to evaluate the neovascular ization in tumor after TACE. Results Lodized oil distributed in and around liver tumor in 48 h. Iodized oil around liver tumor became less at 7th day and disappeared at 14th day. Clearance of iodized oil in liver tumor was observed at 28th day. No vessels were seen from 24 h to 21st day. Smoke-like staining could be observed at 28th day by angiography. Positive rate of VEGF （ % ） and micro vascular density （MVD） was increased in each group. VEGF positive rate from group A to F was （ 24. 0 ± 7.8 ） % , （ 27.0 ± 9. 1 ） % , （36.2±8.4）%, （53.0±9.5）%, （72.4 ±7.3）%, （73.6±12.1）% respectively. Differences in VEGF positive rate among groupB, C, D, E were statistically significant. MVD from group A to F was 10. 8 ± 5.3,12.0 ± 6. 0,12. 6 ± 3.8,24. 3 ± 5.4,38.8 ± 9.5,39.6 ± 6. 2 respectively. Differences in MVD among group C, D, E are statistically significant. Conclusion Lodized oil distributes in largest area in 24-48 h after TACE. VEGF is over-expressed at 7th day after TACE, and reaehes peak at 21st day after TA- CE. Microvessels begin to appear between 7th and 14th day. Small vessels come out at 21st day. Neovas- eularization is obvious at 28th day.

关 键 词：癌 肝细胞 动脉化疗栓塞 碘油沉积 血管内皮因子 微血管密度 

分 类 号：R735.7[医药卫生—肿瘤]