肝动脉灌注贝伐单抗治疗大鼠肝泡状棘球蚴病后血管内皮生长因子的动态变化

Dynamic observation on the serum level of vascular endothelial growth factor in experimental rats with hepatic alveolar echinococcosis after hepatic arterial infusion of bevacizumab treatment

目的观察肝动脉灌注贝伐单抗治疗大鼠肝泡状棘球蚴病(HAE)后血管内皮生长因子(VEGF)生成的动态变化及其对HAE病灶的影响。方法选取40只成功接种HAE的Wistar模型大鼠,分为空白对照组(经肝动脉注射0.9%氯化钠溶液)和实验组(经肝动脉注射贝伐单抗),每组20只。分别于术前及术后7、14、21和28 d鼠尾静脉取血,采用酶联免疫吸附法测血清VEGF、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)水平,并取HAE标本检测贝伐单抗对大鼠HAE病灶的影响。结果从术后7 d开始,实验组血清中VEGF表达降低,与术前及对照组比较差异有统计学意义(P=0.019),术后14 d VEGF表达量持续下降,且以第14天最低,与术前比较差异亦有统计学意义(P<0.01),术后21 d逐渐上升,28 d恢复至正常水平。结论采用贝伐单抗治疗HAE对血管生成有一定的抑制作用,且安全、有效。

Objective To investigate the changes in the serum level of vascular endothelial growth factor （VEGF） in experimental Wistar rats with hepatic alveolar echinococcosis （HAE） after hepatic arterial infusion （HAI） of bevacizumab treatment, and to discuss the efficacy of HAI of bevacizumab for hepatic alveolar echinococcosis. Methods Forty Wistar rats with successfully established HAE were randomly and equally divided into two groups with 20 rats in each group： the control group and the study group. Hepatic arterial infusion of saline was performed in the rats of the control group , while hepatic arterial infusion of bevacizumab was carried out in the rats of the study group. Before and 7, 14, 21 and 28 days after the treatment peripheral blood samples were collected from the tail vein, and the serum levels of VEGF, apartate aminotransferase （AST） and alanine aminotransferase （ALT） were determined by the quantitative sandwich enzyme-linked immunosorbent assay （ELISA）. All the rats were sacrificed 28 days after the treatment. HAE samples were examined to evaluate the effect of bevacizumab on HAE lesions. Results Seven days after hepatic arterial infusion of bevacizumab, serum VEGF expression level in the study group became gradually decreased, and the difference was statistically significant when compared with the preoperative level or with that in the control group （P = 0.019）. Fourteen days after the treatment, the serum VEGF expression level kept going down to its lowest point, and the difference in serum VEGF expression level was statistically significant when compared with the preoperative level （P 0.05）. Conclusion In treating hepatic alveolar echinococcosis, hepatic arterial infusion of bevacizumab has certain inhibitory effect on angiogenesis. This therapy is safe and effective.