羟基磷灰石纳米粒子瘤内注射对兔肝VX_2肿瘤生长的影响  

Inhibitory Effect of Hydroxyapatite Nanoparticles Intratumoral Injection on Liver VX_2 Tumor

作　　者：王雄飞[1] 刘春庆[1] 刘志苏[2] 唐胜利[2] 

机构地区：[1]首都医科大学大兴医院普外一科,北京102600 [2]武汉大学中南医院普外科,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2011年第1期12-15,142,共5页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:30471689)

摘　　要：目的:研究羟基磷灰石纳米粒子(NanoHAP)瘤内注射对兔肝VX2种植瘤生长的影响。方法:将用改良种植法成功接种VX2肝肿瘤的新西兰白兔随机分成4组,每组10只。A组:注入含0.2%羧甲基纤维素钠的生理盐水1ml;B组:注入20g/L5-Fu1ml;C组:注入20g/LNanoHAP溶胶1ml;D组:注入同样浓度5-Fu和NanoHAP的混合液1ml。4组实验动物于注药后第7、14、21天行肝脏B超扫描,测量肿瘤大小;记录生存时间,动物死亡后切取肿瘤、肝组织病理学检查。结果:术后第7、14、21天A组平均肿瘤体积分别为4.93,15.67和52.36cm3;B组:4.16,10.26和18.89cm3;C组:1.43,3.69和9.51cm3;D组为:2.80,3.77和8.46cm3。B、C、D3组肿瘤体积均小于同期对照组,D组肿瘤体积最小。4组动物中位生存期分别为34,41,51和44d。B、C、D3组生存期较对照A组延长。B组与D组无显著性差异,C组较其他3组明显延长。超声监测显示C、D组NanoHAP溶胶瘤内注射时可见肿瘤内强回声光点。多次注射后瘤体内可见钙化样强回声光团。B组在药物注射后第21天可出现低回声的液化坏死区。HE染色后光镜下观察见A组和B组肿瘤组织出现多处片状坏死,C、D组注射区域呈片状坏死,被条索状或片状钙化灶分隔。结论:羟基磷灰石纳米粒子瘤内注射治疗兔VX2肝肿瘤是安全、可行的,对肿瘤生长有明显的抑制作用,亦未见毒性反应。Objective： To study the inhibitory effects of hydroxyapatite nanoparticles （Nano HAP） intratumoral injection on liver VX2 tumor in rabbits.Methods： Forty rabbits with implantation of liver VX2 tumors were randomly divided into four groups and intratumorally injected with 0.2% sodium carboxymethylcellulose （CMC-Na, group A）, 5-Fu （group B）, Nano HAP （group C）, and 5-Fu＋ Nano HAP （group D）.Ultrasound scanning was performed to measure the liver tumor volume at 7, 14, and 21 d respectively after treatment.Survival durations of the animals were recorded.Tumor tissues and liver tissues close to tumor were obtained and examined histologically.Results： The average tumor volumes of group B, C and D were significantly smaller than that of group A the same time after treatment.The life span of group C was longer than other three groups, and there was no statistically difference between group B and group D, while either of the two groups were significantly longer than that of group A.Blood flow was undetectable by color Doppler or power Doppler in group C and group D.Pathological results showed there were obvious intratumoral necrosis in group C and D.Tumor in group B exhibited thoroughgoing necrosis.Conclusion： The results of this investigation showed that hydroxyapatite nanoparticles intratumoral injection was safe and feasible in the treatment of liver tumor.Hydroxyapatite nanoparticles had significant inhibitory effect on liver VX2 tumor growth in rabbits without liver toxicity.

关 键 词：肝肿瘤 羟基磷灰石纳米粒子 瘤内注射 

分 类 号：R735[医药卫生—肿瘤]