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目的观察应用聚N-异丙基丙烯酰胺磁性阿霉素纳米微球(ADM-PNIPAM-Fe_3O_4)对兔VX2肝肿瘤的动脉化疗栓塞治疗作用。方法将肝脏已成功接种VX2肿瘤的新西兰大白兔随机分成4组,每组8只。A组为生理盐水对照组,肝动脉灌注生理盐水10 ml;B组为游离阿霉素组,肝动脉注入阿霉素(1 mg/kg);C组为ADM-PNIPAM组,肝动脉注入ADM-PNIPAM 1．5 mg/ks(约相当于阿霉素1 mg/ks); D组为ADM-PNIPAM-Fe_3O_4并在瘤区外加磁场组,肝动脉注入ADM-PNIPAM-Fe_3O_4 2 mg/kg(相当于阿霉素1 mg/kg),同时在肿瘤表面加磁场。4组实验动物于介入术前1 d,术后14 d行CT肝脏及肺部扫描,测量肿瘤大小,检查肺部转移灶;术后第15天处死,全部实验动物均取肿瘤组织及肺脏作组织病理学检查,C组及D组取胃、脾、肾器官行病理学检查。结果术前1 d各组动物肿瘤体积无明显统计学差异。至术后14 d时,A组平均肿瘤体积为(23．87±7．02)cm~3;B组为(7．70±1．53)cm~3;C组为(4．29±0．25)cm~3;D组为(2．05±0．18)cm~3。B、C、D 3组平均肿瘤体积均小于同期对照A组,B、C、D 3组之间亦有差异,按术后肿瘤体积从大到小的顺序排列依次为B组＞C组＞D组,以ADM-PNIPAM-Fe_3O_4并在瘤区外加磁场组最小。肺转移的发生率A、B、C、D组分别为100%、66．7%、37．5%、12．5%,C、D组肺转移率低于对照A组;与B组相比A组转移率无明显统计学差异,但病理学检查B组转移瘤数目比A组少;肿瘤坏死程度为D组＞C组＞B组＞A组。结论经动脉途径应用ADM-PNIPAM-Fe_3O_4联合外加磁场治疗对兔VX2肝肿瘤生长有较明显的抑制作用。初步肯定ADM-PNIPAM-Fe_3O_4是一种有效的介入化疗栓塞制剂。
Objective To observe the therapeutic effect of poly-N-isopropylacrylamide magnetic doxorubicin nanospheres (ADM-PNIPAM-Fe 3 O 4) on arterial chemoembolization in rabbit VX2 liver tumors. Methods New Zealand white rabbits with liver VX2 tumor inoculation were randomly divided into 4 groups with 8 in each. Group A was saline control group, hepatic artery was infused with 10 ml normal saline, group B was free doxorubicin, hepatic artery was injected with doxorubicin (1 mg / kg), group C was ADM-PNIPAM group, -PNIPAM 1.5 mg / ks (approximately equivalent to doxorubicin 1 mg / ks); group D ADM-PNIPAM-Fe 3 O 4 and implanted with magnetic field in the tumor area; ADM- PNIPAM-Fe 3 O 4 2 mg / kg Equivalent to doxorubicin 1 mg / kg), while the magnetic field in the tumor surface. Four groups of experimental animals were examined by CT liver and lung scan on the first day before operation and 14 days after operation. The size of the tumor was measured and the lung metastases were examined. On the 15th day after operation, all the experimental animals were sacrificed for tumor tissue and lung Histopathological examination, C group and D group take pathological examination of the stomach, spleen and kidney. Results There was no significant difference in tumor volume between the groups before operation on the first day. The average tumor volume in group A was (23.87 ± 7.02) cm ~ 3 at 14 days after operation, (7.70 ± 1.53) cm ~ 3 in group B and (4.29 ± 0.25) cm ~ 3; group D was (2.05 ± 0.18) cm ~ 3. The average tumor volume in groups B, C and D were less than those in control group A, B, C, and D groups, and the order of the tumor volume in descending order was B> C> D group, with ADM-PNIPAM-Fe_3O_4 and applied in the tumor area minimal magnetic field group. The incidence of lung metastasis was 100%, 66.7%, 37.5% and 12.5% in groups A, B, C and D, respectively. The lung metastasis rates in groups C and D were lower than those in group A There was no significant difference in the metastasis rate between group A and group B, but the number of metastases in group B was less than that in group A; the degree of tumor necrosis was group D> C group> B group> A group. Conclusion ADM-PNIPAM-Fe_3O_4 combined with magnetic field therapy can significantly inhibit the growth of VX2 liver tumor in rabbits. Preliminary confirmed ADM-PNIPAM-Fe_3O_4 is an effective interventional chemoembolization preparation.