兔胰腺移植瘤纳米刀、冷冻、射频的对比研究  

A comparative study of nanoknife,cryoablation,and radiofrequency ablation for treatment of pancreatic cancer xenograft in rabbits

作　　者：宁周雨[1] 王鹏[1] 陈颢[1] 解婧[1] 林钧华[1] 朱晓燕[1] 陈其文[1] 徐立涛[1] 宋利斌[1] 高嵩[1] 姜峰 孟志强[1] 

机构地区：[1]复旦大学附属肿瘤医院中西医结合科,上海200032 [2]潍坊诸城中医医院肿瘤科,潍坊262200

出　　处：《第二军医大学学报》2016年第1期10-16,共7页Academic Journal of Second Military Medical University

摘　　要：目的通过研究胰腺移植瘤不可逆电穿孔(irreversible electroporation,IRE,俗称"纳米刀")、冷冻、射频术后的肿瘤凋亡、机体免疫反应及血管生成因子情况,观察不同微创技术对胰腺移植瘤的抗肿瘤效果。方法兔胰腺移植瘤模型8只,并随机分为模型对照组、纳米刀治疗组、冷冻治疗组及射频治疗组,每组2只。动态观察治疗过程中新西兰大白兔的生命体征,于治疗后第1天全部处死,分离血浆及血清进行检测,H-E染色观察移植瘤组织形态学改变,免疫组织化学方法检测Bcl-2、HSP70和VEGF在胰腺癌移植瘤中的表达,Tunnel法检测细胞凋亡。结果各组实验兔术后均存活。肉眼观肿瘤边界清晰,触之质地较硬,各组治疗区域可见明显凝固性坏死改变。H-E染色显示治疗组坏死区域和正常区域边界清晰,以纳米刀组为著。各组坏死边缘区可见大量红细胞以及炎症细胞浸润,冷冻及射频术区仍可见部分存活细胞。Tunnel结果显示,射频治疗可以明显增加胰腺癌细胞凋亡。与模型对照组相比,各治疗组血浆的Caspase-3、TNF-α及VEGF水平升高;术区Bcl-2及VEGF因子表达降低,HSP70表达升高。术后血清学检测结果显示仅纳米刀治疗后新西兰大白兔的肌酸激酶水平升高,冷冻及射频组未见升高;肌钙蛋白、肝肾功能及血清淀粉酶未见异常。结论纳米刀、冷冻、射频治疗兔胰腺移植瘤时,均可能通过诱导细胞凋亡、产生特异的抗肿瘤免疫效应及抑制血管生成来抑制兔胰腺移植瘤的生长,且治疗方法安全、有效。纳米刀在激发机体肿瘤免疫和保护周围重要脏器上有一定的优势。Objective To investigate the apoptosis, immunity response and angiogenesis factor changes in rabbits with pancreatic cancer xenografts after treatment with irreversible electroporation （IRE, commonly known as nanoknife）, cryoablation, or radiofrequency ablation （RFA）, and to observe the antitumor effects of the above minimally invasive techniques for pancreatic cancer xenografts. Methods Eight pancreatic cancer xenograft model rabbits were randomly divided into the control, IRE, cryoablation, and RFA groups, with each group containing 2 rabbits. The vital signs of the animals were observed during the treatment and all the rabbits were executed on the next day after treatment. The serum samples were collected to examine the liver, kidney function and creatine kinase levels; and ELISA method was used to detect the cardiac troponin I（CTnI）, Caspase-3, tumor necrosis factor-~ （TNF-a） and vascular endothelial growth factor（VEGF） levels in the plasma. Morphological changes of the tumor tissues were subjected to H-E staining, and Tunnel assay was used to detect the apoptosis of tumor cells. Immunohistochemistry method was applied to detect Bcl-2, HSP70 and VEGF expression in pancreatic cancer xenograft tissues. Results All the rabbits survived after treatment. The tumors had a clear border and were hard in texture. Obvious coagulative necrosis areas were seen in the treatment areas in each treatment group. H-E staining showed a clear borderline between the necrotic and normal areas, which was especially true in the IRE group. A large number of red blood cells and inflammatory cell infiltration were seen around the border of the necrosis in each group, with some live cells seen in the cryoablation and RFA groups. Tunnel assay showed that RFA significantly increased the apoptosis in pancreatic cancer cells compared with the other two treatment groups. The plasma Caspase-3, TNF-a and VEGF levels were increased in each treatment group. Bcl-2 and VEGF expression was decreased and HSP70 expression was incr

关 键 词：胰腺肿瘤 异种移植 纳米刀 冷冻消融 射频消融 细胞凋亡 肿瘤免疫 安全性 

分 类 号：R735.9[医药卫生—肿瘤]