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

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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 effect of NanoHAP intratumoral injection on the growth of hepatic VX2 implanted tumor in rabbits. Methods: New Zealand white rabbits successfully inoculated with modified VX2 liver tumor were randomly divided into 4 groups with 10 in each group. Group A: injecting 1 ml saline containing 0.2% sodium carboxymethylcellulose; Group B: injecting 20 g / L 5-Fu 1 ml; Group C: injecting 1 ml 20 g / L nanoanoha sol; Group D: injecting 5-Fu and NanoHAP Mix 1ml. Four groups of experimental animals underwent hepatic B-scan scanning on the 7th, 14th and 21st day after injection, and the tumor size was measured. The survival time was recorded and the tumors were excised and the pathological examination of the liver was performed. Results: The mean tumor volume of group A was 4.93, 15.67 and 52.36 cm3 respectively on the 7th, 14th and 21st day after operation. In group B, 4.16, 10.26 and 18.89cm3, in group C were 1.43, 3.69 and 9.51cm3 respectively, while in group D was 2.80 , 3.77 and 8.46 cm3. The tumor volume in groups B, C and D3 were all less than that of the control group in the same period, and the tumor volume in group D was the smallest. The median survival of the 4 groups was 34, 41, 51 and 44 days, respectively. Group B, C, D3 survival than the control group A extended. There was no significant difference between group B and group D. Group C was significantly longer than the other three groups. Ultrasound monitoring showed that intracancerous echogenic spots were found in intracavitary tumors of NanoHAP in C and D groups. Multiple injections can be seen within the tumor after calcification like strong echo light group. In group B, hypoechogenic liquefied necrotic area appeared on the 21st day after drug injection. After HE staining, many tumor necrosis appeared in group A and group B, and necrosis was observed in group C and group D, and were separated by cord - like or lamellar calcifications. Conclusion: The treatment of rabbit VX2 hepatic tumor by intratumoral injection of hydroxyapatite nanoparticles is safe and feasible, and has obvious inhibitory effect on tumor growth and no toxic reaction.
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