摘要目的:观察索拉非尼对肝泡状棘球蚴小鼠模型病灶及血管生长因子的影响。方法:选用100只体重(20±4)g的健康雌性昆明小鼠，通过腹腔注射泡状棘球蚴原头节建立泡状棘球蚴感染模型。饲养6周后分为5组，每组15只，分别给予温盐水、阿苯达唑(100 mg/kg)及高剂量(100 mg/kg)、中剂量(50 mg/kg)和低剂量(30 mg/kg)索拉非尼灌胃，持续6周。末次给药后取小鼠眼球血及肝泡状棘球蚴组织，称取小鼠体重和病灶重量，采用酶联免疫吸附试验和蛋白质印迹法检测小鼠血清及病灶组织中缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子-A(VEGF-A)、血管内皮生长因子受体-2(VEGFR-2)的浓度及表达水平。结果:盐水组、阿苯达唑组以及低、中、高剂量索拉非尼组小鼠的体重比较差异无统计学意义( F＝0.43， P＝0.784)，上述各组小鼠的病灶重量/小鼠体重比分别为(0.057±0.009)、(0.031±0.005)、(0.033±0.005)、(0.031±0.005)、(0.031±0.005)，盐水组高于其他4组，差异有统计学意义(均 P<0.05)。蛋白质印迹法检测盐水组中HIF-1α、VEGF-A、VEGFR-2、CD31、CD34的相对表达水平均高于阿苯达唑组及索拉非尼的高、中、低剂量组，差异均有统计学意义(均 P<0.05)，中、高剂量索拉非尼组的上述蛋白的相对表达水平低于阿苯达唑组，同时高剂量索拉非尼组的上述蛋白的相对表达水平也低于中剂量索拉非尼组，差异均有统计学意义(均 P<0.05)。酶联免疫吸附法检测各组小鼠血清中HIF-1α、VEGF-A、VEGFR-2的浓度水平与蛋白质印迹法检测结果一致。 结论:索拉非尼通过抑制泡状棘球蚴小鼠病灶的血管生长因子的表达而抑制泡状棘球蚴病灶的增殖。

abstractsObjective:To observe the effects of sorafenib on the lesions and vascular growth factors in the mouse model of hepatic alveolar echinococcosis.Methods:One hundred healthy female Kunming mice weighing (20±4) g were used to establish a model of alveolar echinococcosis infection by intraperitoneal injection of alveolar echinococcosis protoscoleces. After 6 weeks of feeding, the rats were divided into 5 groups, 15 rats in each group, which were given warm saline, albendazole (100 mg/kg), and sorafenib at high-dose (100 mg/kg), middle-dose (50 mg/kg) and low-dose (30 mg/kg) by gavage for 6 weeks, respectively. Eyeball blood and hepatic alveolar echinococcosis tissue were collected from the mice after the last administration, and the body weight of the mice and the lesion weight were weighed. The concentrations and expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor-2 (VEGFR-2) in serum and lesion tissues were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting.Results:There was no statistically significant difference in the body weight of mice among the saline group, albendazole group and low-dose, medium-dose and high-dose sorafenib groups ( F=0.43, P=0.784). The ratios of lesion weight to body weight in the above groups were (0.057±0.009), (0.031±0.005), (0.033±0.005), (0.031±0.005), and (0.031±0.005), respectively. The saline group had a higher ratio than the other four groups, and the differences were statistically significant (all P<0.05). The relative expression levels of HIF-1α, VEGF-A, VEGFR-2, CD31 and CD34 detected by Western blotting in the saline group were all higher than those in the albendazole group and the high-dose, medium-dose and low-dose sorafenib groups, and the differences were statistically significant (all P<0.05). The relative expression levels of the above proteins in the medium-dose and high-dose sorafenib groups were lower than those in the albendazole group, and the relative expression levels of the above proteins in the high-dose sorafenib group were also lower than those in the medium-dose sorafenib group, and the differences were statistically significant (all P<0.05). The concentration levels of HIF-1α, VEGF-A and VEGFR-2 in serum of mice in each group detected by ELISA were consistent with those detected by Western blotting. Conclusion:Sorafenib inhibits the proliferation of alveolar echinococcosis in mice by suppressing the expression of angiogenic factors in alveolar echinococcosis lesions.