新型温敏纳米凝胶经肝动脉栓塞兔VX2肿瘤的可行性研究

Study of the Treatment Effect of Transcatheter Arterial Embolization with Novel Temperature Sensitive Nanogel( PIB) for VX2 Tumor of Liver in Rabbits

目的采用CT增强及病理学方法评估新型温敏纳米凝胶(PIB)经肝动脉栓塞治疗兔肝VX2肿瘤的效果,并探讨其作为血管栓塞剂的可行性。方法 45只健康日本大耳白兔,肝脏左叶植入VX2肿瘤组织块建模,将建模成功的荷瘤兔随机分为三组,PIB组,碘油组(DY组)及生理盐水组(NS组)各15只行经肝动脉栓塞治疗,于术前1天、术后3天、7天、14天时间点检测各组实验兔肝功能,同时行CT增强扫描,测量栓塞前后各组肿瘤体积变化并计算肿瘤体积增长率,观察肿瘤形态学改变同时结合病理学方法验证其治疗效果。结果术前1天,PIB、DY及NS各组间肝功能差异无统计学意义(P>0.05)。兔肝VX2肿瘤经肝动脉栓塞术后3天,PIB组、DY组的肝功能(ALT、AST)较NS组明显升高。对于肝功能ALT,PIB组、DY组分别与NS组差异有显著统计学意义(P<0.05)。但PIB组及DY组组间差异无统计学意义(P>0.05);对于肝功能AST,PIB组、DY组、NS组三组间差异均有统计学意义(P<0.05)。术后7天,三组间的差异无显著统计学意义(P>0.05)。术后14天,PIB、DY及NS三组间肝功能差异与术后3天各组统计学结果相同(P<0.05)。术前1天三组肿瘤体积大小的差异无显著统计学意义;术后3天、7天及14天,PIB、DY、NS三组肿瘤体积的差异均有统计学意义(P_3<0.05;P_7<0.05;P_(14)<0.05),且分别为术后3天PIB组肿瘤体积增大明显,与DY、NS组差异均有统计学意义,术后7天NS组肿瘤体积增大明显,分别与PIB、DY组差异有统计学意义。栓塞术后7天,PIB及DY组肿瘤体积增长率均较NS组低,差异有统计学意义(P<0.05),但两组间差异无显著统计学意义(P>0.05),14天后三组间肿瘤体积及体积生长率均有显著性差异(P<0.05)。影像学上的环形强化灶均为病理切片下的肿瘤细胞组织,病理所见肿瘤范围与影像学测量大体一致。结论 PIB兔肝动脉介入栓塞治疗安全有效,可明显抑制肿瘤生长,其长期抑瘤效果较碘油佳,作为血管栓塞剂可行性好。

Objective To evaluate the treatment effect of transcatheter arterial embolization （TAE） with temperature sensitive nanogel for VX2 tumor of liver in rabbits by CT enhance scan and histopathology,and discussed the feasibility as vascular embolization agent. Methods 45 Japanese white rabbits were randomly divided into three groups with 15 rabbits in each group after VX2 tumor tissue block successful implantation in the left lobe of the liver. Temperature-sensitive nano- gel p（N-isopropyl-acrylamide-co-butyl methylacrylate） （PIB group） , lipiodol （ DY group） and saline（ NS group）. VX2 tumor-bearing rabbits underwent liver function test and CT enhance scanning before and after TAE 3 days, 7 days and 14 days. The tumor volume and the tumor growth rate were calculated, the morphological changes of tumor also were observed. And the treatment effect was observed by pathological method. Results Before operation, there was no significant differ- ence in the liver function between the three groups （ PIB group, DY group, NS group） （ P 〉 0.05 ）. After TAE 3 days, the function of liver （ALT, AST） both PIB group and DY group increased, for liver function ALT, compared with NS group,PIB group and DY group had significantly different （P 〈0. 05 ） while there was no significant difference between them （P 〉 0.05） ; for liver function AST, PIB, DY and NS group all improved significantly （P 〈 0.05 ）. There was no significant difference in the liver function after TAE 7 days （ P 〉 0.05）, and there were the same statistical results between post-14- day and post-3-day （P 〈 0.05 ）. Before operation, there was no significant difference in the tumor volume between the three groups （P 〉0 . 05）. After TAE 3 days ,7 days and 14 days, PIB, DY and NS group all improved significantly （P3 〈 0.05 ; P7 〈 0.05 ; P14 〈 0.05）. After TAE 7 days, both PIB group and DY group have significant differences in tumor growth rate compared to NS group （P 〈0. 05）, and the growth rate of tumor volume was significantly differences among the three groups after TAE 14 days（P 〈 0.05 ）. The ring-enhancement area tissue of image was composed of tumor cells of pathological section. It＇ s in line between pathology and CT images for the measure of tumor volume. Conclusion It is ef- fective for the interventional embolization of rabbit liver VX2 tumor with temperature sensitive nano gel, it has better effects on inhibiting tumor growth than the iodine oil. So is a safety and permanent agent can be used as blood vessel embolic ma- terial.