兔VX_2肝癌模型纳米磁微粒栓塞热疗初步研究

Hyperthermia after nano magnetic particles embolization VX_2 rabbit liver tumor model

目的：观察磁性微粒栓塞热疗对 VX2兔肝癌的疗效。方法40只大白兔制成 VX2模型后等分成四组：对照组（A组）、碘油栓塞组（B组）、碘油＋磁性微粒组（C组）、磁热疗组（D组）。制备肿瘤模型后14 d，B、C、D组经股动脉逆行插管行肝动脉造影及栓塞。栓塞后第2天，B组3只和D组全部动物于振荡磁场（alternating magnetic field，AMF）下接受磁热疗，实时测定动物肿瘤中心、肿瘤边缘及正常肝组织3个部位温度变化。治疗前后查血常规、肝肾功能。治疗后14 d处死全部动物，开腹观察肿瘤情况并行病理检查。结果治疗前四组肿瘤体积分别为（1.6±1.5）、（2.5±2.5）、（2.7±1.6）、（3.5±2.6）cm3，各组肿瘤大小差异无统计学意义（F＝1.247，P＝0.308）。AMF下，B组3个部位平均温度与磁热疗前相应部位温度比较差异无统计学意义（F 瘤心＝0.01， P 瘤心＝0.981；F 瘤缘＝0.618，P 瘤缘＝0.476；F 正常肝＝0.217，P 正常肝＝0.665）；D组3个部位热疗前温度分别为（35.4±1.7）、（35.9±1.8）、（36.1±1.4）℃，差异无统计学意义（F＝1.038，P＝0.413）；热疗开始后7～26 min D组肿瘤中心及边缘温度与B组相应部位及D组正常肝组织的温度差异有统计学意义（FB-D 瘤心＝5.431，PB-D 瘤心＝0.041；FB-D 瘤缘＝9.744，PB-D 瘤缘＝0.011；FD 组3个部位＝8.379， PD组3个部位＝0.002）；D组肿瘤边缘温度最高可达46℃。术后14 d，四组肿瘤体积分别为（31.4±20.6）、（26.7±18.2）、（28.7±9.1）、（25.8±13.9）cm3，各组之间差异无统计学意义（F＝0.218，P＝0.883），但D组肿瘤体积最小。血常规、肝肾功能于治疗后7d恢复正常水平。结论经肝动脉磁性微粒栓塞后磁热疗治疗VX2兔肝脏肿瘤是安全可行的，可进一步深入研究。

Objective To observe the effect of hyperthermia and the influence of heat to surrounding organs of VX2 rabbit liver cancer model exposed to alternating magnetic field after embolized with nanomagnetic particles. Methods 40 rabbits with VX2 tumor were divided into four groups equally. Group A as control group receive no treatment, group B embolized with lipiodol embolization only, group C embolized with lipiodol plus magnetic particles and group D exposed to alternating magnetic field after embolized with lipiodol plus nanomagnetic particles. 14 days after the tumor transplanted, opened the abdomen to observe the size and shape of the tumor. Then trans-femoral retrograde approach of hepatic arterial catheterization was used in group B, C and D to do angiography and embolization. The next day, three models of group B and all of group D were exposed to alternating magnetic field, the temperature in the center of tumor, the edge of tumor and normal liver parenchyma were measured simultaneously. Venous blood of each animal was get just before the operation, the blood routine and the function of liver and kidney was examined. 14 days later, all animals will be killed to observe the change of tumor in the liver and the condition of the abdomen, the pathology examination will also be done. Results The volume of tumor among four groups[（1.6±1.5）, （2.5±2.5）, （2.7±1.6）, （3.5±2.6）cm3] had no significant difference before operation （F=1.247, P=0.308）. The three different positions temperature of group B under AMF had no significant difference compared to pre-operation temperature （Fcenter=0.01, Pcenter=0.981; Fedge=0.618, Pedge=0.476; Fnormol=0.217, Pnormal=0.665）. Three points basic temperature of group D （35.4±1.7 ℃, 35.9±1.8℃and 36.1±1.4℃） was without significant difference （F=1.038, P=0.413）. 7 to 26 minutes after hyperthermia, the center and the edge temperature of tumor in group D had significant difference with corresponding positions of group B and liver parenchyma of group D（FB-D center=5.431, PB-D center=0.041;FB-D edge=9.744, PB-D edge=0.011; FD =8.379, PD=0.002）. The highest temperature at the edge of tumor of group D could be reach 46℃. 14 days later, the tumor volume of 4 groups was （31.4±20.6）, （26.7±18.2）, （28.7±9.1）, （25.8±13.9）cm3 respectively, which without significant difference with each other （F=0.218, P=0.883）, but the tumor volume of Group D was the smallest. The blood routine and liver function restored to normal seven days after therapy. Conclusions It is feasible to cure the VX2 tumor under an alternating magnetic field after nanomagnetic particles embolization without significant effect on surrounding normal liver parenchyma.