活血、破血药对ApoE基因缺陷小鼠AS模型主动脉VEGF及VEGFR-2表达的影响

Effects of Blood-activating and Blood-breaking Medicines on VEGF and VEGFR-2 Expressions in Aortic Arteries of Apo E Gene Dificient Mice AS Models

目的探讨活血药(川芎、当归)、破血药(三棱、莪术)对载脂蛋白E(Apo E)基因缺陷小鼠主动脉血管内皮生长因子(VEGF)及血管内皮生长因子受体-2(VEGFR-2)蛋白表达的影响。方法 64只8周龄Apo E基因缺陷小鼠复制动脉粥样硬化(AS)模型,造模成功后随机分为6组:模型对照组(简称A组)、阿托伐他汀钙组(简称B组)、低剂量活血药组(简称C组)、高剂量活血药组(简称D组)、低剂量破血药组(简称E组)、高剂量破血药组(简称F组)。灌胃给药,连续4周,处理动物。采用酶联免疫吸附法(ELISA)检测血清中VEGF含量;采用免疫组化法检测主动脉组织VEGF及VEGFR-2蛋白表达。结果在ELISA法检测VEGF含量方面,与A组比较,D、E、F组血清中VEGF含量均降低(P<0.05或P<0.01);与C组比较,D、F组血清中VEGF含量均降低(P<0.05);D组与F组组间无差异(P>0.05)。在免疫组化法检测VEGF及VEGFR-2蛋白表达方面,与A组比较,C、D、F组主动脉均减少(P<0.05或P<0.01);与C组比较,D、F组主动脉均减少(P<0.01);D组与F组组间无差异(P>0.05)。结论活血药(当归、川芎)、破血药(三棱、莪术)具有抗动脉粥样硬化的作用,其作用机制可能与抑制主动脉VEGF及VEGFR-2蛋白表达有关。

Objective To obeserve the effects of blood-activating medicines （angelica sinensis and ligusticum wallichii） and blood-breaking medicines （rhizoma sparganii and curcuma zedoary） on vascular endothelial growth factor （VEGF） and vascular endothelial growth factor receptor （VEGFR-2） of apolipoprotein E （ApoE） gene deficient mice models. Methods 64 ApoE gene deficient mice atherosclerosis （AS） models at 8-weeks of age were randomly divided into 6 groups： model group （group A）, atorvastatin group （group B）, low dose of blood- activating group （group C））, high dose of blood-activating group （group D）, low dose of blood- breaking group （group E））, high dose of blood-breaking group （group F）. After 4 weeks＂ drug gastric perfusion, the mice were killed. The VEGF levels in serum were detected by ELISA. The aortic tissue VEGF and VEGFR-2 expression were tested by immunohistochemical staining. Results Compared with the group A, the VEGF levels in serum of group D, E and F decreased （P〈0.05 or P〈0.01）; Compared with the group C, the VEGF levels in serum of group D and F decreased （P〈0.05）; There was no significant difference between group D and F （P〉 0.05）. Compared with the group A, the aortic VEGF and VEGFR-2 expression in group D, E and F reduced （P〈0.05 or P〈0.01）; Compared with the group C, the VEGF and VEGFR-2 expression decreased （P〈0.01）; There was no significant difference between group D and F（P〉0.05）. Conclusion Blood-activating（angelica sinensis and ligusticum wallichii） and blood-breaking medicines （rhizoma sparganii and curcuma zedoary） showed the anti-atherosclerotic effect, its mechanism could be related with the inhibition of VEGF and VEGFR-2 expression in aorta.