碘油磁液经肝动脉栓塞热疗兔VX2肝癌的实验研究

目的 探讨碘油磁液经肝动脉栓塞热疗术对荷瘤兔肝、肾功能的影响及其疗效.方法 VX2兔肝癌模型32只,数字表法随机等分成4组:碘油磁液栓塞热疗组(A组)、碘油磁液栓塞组(B组)、单纯碘油栓塞组(C组)、对照组(D组).A、B两组实验兔经肝动脉注入碘油磁液0.5～0.8 ml栓塞病灶,C组实验兔仅用碘油栓塞.栓塞后仅A组实验兔在交变磁场下诱导热疗.实验兔分别于栓塞或栓塞热疗术前1 d和术后1、7、14 d经耳缘静脉取血,行肝、肾功能检查.肝功能指标选取丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST),肾功能指标选取血清尿素氮(BUN)和血清肌酐(Cr).栓塞术前、术后即刻、术后7、14 d行CT扫描并随访,观察碘油磁液或碘油在瘤内沉积分布情况并分别测量肿瘤大小.术后14 d处死实验兔,完整切取肝脏、脾、肾和肺,作病理检查.各组测量数据以重复测量方差分析进行统计学分析.结果 A组实验兔术前1 d和术后1、7、14 d ALT分别为(43.9±19.0)、(795.1±327.1)、(67.0±9.3)、(41.9±10.8)U/L,AST分别为(50.2±13.6)、(1011.2±655.9)、(62.4±24.1)、(51.6±7.9)U/L;B组ALT分别为(45.0±19.1)、(580.8±160.4)、(67.2±31.0)、(47.6±7.8)U/L,AST分另U为(52.9±20.3)、(735.2±186.1)、(57.9±24.8)、(50.9±9.8)U/L;C组ALT分别为(47.4±14.6)、(558.5±167.8)、(63.5±21.9)、(48.0.±9.3)U/L,AST分别为(51.8±9.5)、(752.5±112.0)、(56.5 ±20.6)、(51.4±8.6)U/L;术后1 dALT和AST较术前和D组明显升高(P值均<0.01),术后7、14 d所测值与术前比较差异无统计学意义.栓塞术前后4组实验兔BUN和Cr值组间和组内比较,差异均无统计学意义.术后7 d CT示A、B、C 3组瘤区碘油磁液和碘油沉积分布与栓塞或栓塞热疗前相比无明显变化.术后14 d CT示A组瘤区碘油磁液沉积更集中、密实,B、C两组共5例肿瘤瘤周碘油磁液或碘油移位、部分消失.术后14 d,A组肿瘤体积(6.1±0.6)cm~3]较术前(7.8±1.4)cm~3]平均缩小约21.7%(F=17.56,P<0.01),而术前B、C两组肿瘤体积分别为(7.9±1.1)、(7.8±0.9)cm~3,治疗后14 d分别为(9.1±0.8)、(9.3±1.0)cm~3,较术前平均增大16.2%、18.9%(F值分别为25.23、55.50,P值均<0.01).病理检查,栓塞14 d后,A组肿瘤坏死均达80%以上,B、C两组肿瘤坏死约30%~50%.结论 碘油磁液对兔VX2肝癌行选择性肝动脉栓塞热疗是安全有效的,具有可行性.

Experimental study on rabbits bearing VX2 liver tumor by hyperthermia following transarterial embolization with magnetic nanoparticles suspended in lipiodol

Objective To investigate the changes in function of liver and kidney of the rabbits bearing VX2 liver tumor after transarterial embolization and hyperthermia with magnetic nanoparticles suspended in lipiodol(MN-L) and its therapeutic effect Methods Thirty-two rabbits bearing VX2 liver tumor were randomly divided into four groups and each group contained 8 rabbits The four groups were MN-L embolization hyperthermia group (Group A), MN-L embolization group(Group B),Lipiodol embolization group(Group C), and Control group (Group D), Each rabbit in Group A and B was embolized with 0.5-0.8 ml MN-L through hepatic artery, while each rabbit in Group C was embolized with 0.5-0.8 ml lipiodol.Hyperthermia in alternating magnetic field was performed in Group A after embolization.The remaining groups did not undergo hyperthermia.The rabbits in control group were not treated.The function of liver and kidney of all the animals was measured 1d before embolization,and 1,7,and 14 d after embolization/hyperthermia respectively.Alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) were used to reflect the function of liver,and blood urea nitrogen(BUN) and creatinine (Cr) were used to reflect the function of kidney.CT was performed on all of subjects before and after embolization to determine the embolization effect and the tumor size, and follow-up CT was performed weekly.All of subjects were sacrificed 14 days after embolization/hyperthermia, and their livers, spleens, kidneys and lungs were removed for histopathology examination.The data from every group were analyzed using analysis of variance of repeated measure data.Results On 1 day before embolization and 1,7, and 14 d after embolization/hyperthermia, the function of liver of the rabbits was as follows:Group A:ALT was (43.9±19.0),(795.1±327.1),(67.0±9.3), and(41.9±10.8) U/L respectively,and AST was (50.2±13.6),(1011.2±655.9),(62.4±24.1),and(51.6±7.9) U/L respectively; Group B: ALT was(45.0±19.1),(580.8±160.4),(67.2±31.0),and(47.6±7.8) U/L respectively, and AST was (52.9±20.3),(735.2±186.1),(57.9±24.8),and (50.9±9.8) U/L respectively; Group C: ALT was (47.4±14.6),(558.5±167.8),(63.5±21.9),and (48.0±9.3) U/L respectively, and AST was (51.8±9.5),(752.5±112.0),(56.5±20.6),and(51.4±8.6) U/L respectively.Both ALT and AST mean values of the rabbits were significantly elevated 1 d after embolization/hyperthermia in Group A, B and C, and the data showed statistically significant difference comparing with that before therapy and that of Group D 1 d after therapy (P<0.01).The function of liver showed no statistically significant difference between 7 or 14 days after embolization and 1 day before embolization in Group A,B and C. BUN and Cr mean values in pre-embolization and post-embolization rabbits revealed no statistically significant difference in group A, B, C and D.The MN-L /lipiodol were deposited in the tumor when it was injected, which was validated by CT.To compare with immediate CT after embolization, the MN-L deposited in tumors was not significantly different on CT 7 d after embolization .On the 14 th day after treatment,the MN-L deposited in tumors became concentrative and compact in Group A, while the MN-L/lipiodol deposited at the rim of tumors disappeared on CT in five rabbits of Group B and C.And the tumor size decreased by 21.7% compared to that before treatment in Group A from (7.8±1.4)cm~3 to(6.1±0.6) cm~3,F=17.56, P<0.01], but tumor size increased by 16.2% and 18.9% in Group B and C respectively from (7.9±1.1)and (7.8±0.9)cm~3 to (9.1±0.8) and (9.3±1.0)cm~3, F =25.23,55.50, P<0.01].Histopathologically, the tumor of Group A was necrotic for at least 80% 14 day after embolization, while the tumor of Group B and C was necrotic for 30% to 50% .Conclusion Transarterial embolization and hyperthermia with MN-L is safe, effective and feasible on the rabbits bearing VX2 liver tumor.