目的：探讨采用血管内皮细胞生长因子（VEGF）缩短SD大鼠Walker-256肝转移瘤成模时间的安全性与可行性，为抗VEGF靶向药物的研究提供更实用的模型。方法：将SD大鼠随机分为3组，每组各15只。生理盐水（NS）模型组：于建模前1周开始尾静脉注射生理盐水0．1 mL/d；20 mg/L VEGF模型组：于建模前1周开始尾静脉注射20 mg/L VEGF（0．1 mL/d）；40 mg/L VEGF模型组于建模前1周开始尾静脉注射40 mg/L VEGF（0．1 mL/d）。各组均注射至建模当天。建模方法：暴露大鼠肝脏，将瘤块种植于肝包膜下。分别于建模后3 d、1周和2周用磁共振成像（MRI）观察肿瘤生长情况，并记存活时间。结果：建模成功，肝内肿块HE染色符合恶性肿瘤特点。大鼠肝脏MRI表现：肿块呈结节状，T2WI呈稍高信号，显示更为清楚，腹水于T2WI呈高信号。 NS模型组和20 mg/L VEGF模型组各有1只动物于建模后1 d死亡，40 mg/L VEGF模型组有3只于建模1周后死亡。建模后3 d各组可观察到肿块的大鼠数分别为：NS模型组0只，20 mg/L VEGF模型组7只，40 mg/L VEGF模型组10只；建模后1周各组可观察到肿块的大鼠数分别为：NS模型组3只，20 mg/L VEGF模型组14只，40 mg/L VEGF模型组13只；建模后2周各组可观察到肿块的大鼠数分别为：NS模型组12只，20 mg/L VEGF 模型组14只，40 mg/L VEGF模型组10只。20 mg/L VEGF模型组和40 mg/L VEGF模型组分别与NS模型组相比，3 d可观察到成瘤的老鼠数目差异均有统计学意义（P＜0．05）。 NS模型组与20 mg/L VEGF模型组大鼠存活时间差异无统计学意义（P＞0．05），40 mg/L VEGF模型组存活时间短于NS模型组（P＜0．01）。结论：20 mg/L VEGF能缩短SD大鼠肝转移瘤成模时间，对其存活时间无显著影响，且相较于传统模型，更适合应用于抗VEGF靶向药物的研究。%AIM:To evaluate the safety and feasibility of using vascular endothelial growth factor (VEGF) in the establishment of Walker-256 transplanted liver cancer model .METHODS: SD rats ( n =45) were divided into 3 groups:via the caudal vein, the rats in normal saline (NS) group were injected with 0.9%sodium chloride (0.1 mL/d), the rats in 20 mg/L VEGF group were injected with 20 mg/L VEGF (0.1 mL/d), and the rats in 40 mg/L VEGF group were injected with 40 mg/L VEGF (0.1 mL/d).All the injection began 1 week before transplantation of liver cancer , and stopped on the day the cancer model was established .Prepared tumor tissue was transplanted into the subcapsular space of the liver.Three days, 1 week and 2 weeks after the transplantation, magnetic resonance imaging (MRI) was performed for analyzing the tumor growth and the characteristics .The overall survival of the rats was also recorded .RESULTS:Success-ful establishment of Walker-256 transplanted liver cancer model was achieved .Among 45 rats, 1 rat died 1 d after implan-ting the tumor both in NS group and 20 mg/L VEGF group, while 3 rats died in 40 mg/L VEGF group 1 week after building the model, mainly because of the progression of tumors .Three days after modeling,the numbers of the rats in which the tumor was positively detected by MRI in 3 groups were 0, 7 and 10, respectively;1 week after modeling, those were 3, 13 and 13, respectively;2 weeks after modeling,those were 12, 13 and 10, respectively.Between NS group and 20 mg/L VEGF group, the statistical significance existed in the number of the rats in which the tumor was positively detected by MRI after 3 d of implanting, so did the NS group and 40 mg/L VEGF group.No statistical significance in the overall survival time between NS group and 20 mg/L VEGF group (P>0.05) was observed, but the significance existed between 40 mg/L VEGF group and NS group (P<0.01).CfONCLUSION:The application of VEGF at dose of 20 mg/L and 0.1 mL/d shortens the time to establish the transplanted liver cancer model without influence on the overall survival , which is a safe, feasible and efficient way, and is more suitable for anti-VEGF drug investigation.
展开▼
