VEGF在SD大鼠Walker-256肝转移瘤模型建立中的应用

 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。

Role of VEGF in establishment of Walker-256 transplanted liver cancer model in SD rats

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：Successful establishment of Walker-256 transplanted liver cancer model was achieved. Among 45 rats, 1 rat died 1 d after implanting 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.