邓老冠心方对ApoE^(-/-)小鼠动脉粥样硬化斑块内新生血管及VEGF信号通路的影响

Effects of Denglao Guanxin formula on the plaque angiogesis and the unstable plaque VEGF signal channel in ApoE Knock-out mice with atherosclerosis

目的研究邓老冠心方防治动脉粥样硬化(AS)不稳定斑块发生发展的可能作用机制。方法以高脂饲料喂养雄性ApoE^(-/-)小鼠13周,复制AS小鼠模型。将模型小鼠随机分成模型组、邓老冠心方高剂量组、低剂量组、辛伐他汀组,分别给予蒸馏水、邓老冠心方和辛伐他汀干预12周。胸主动脉组织切片免疫组化观察斑块内新生血管标志物白细胞分化抗原(CD)34阳性表达,检测各组血管内皮生长因子(VEGF)、血管内皮生长因子受体-2(VEGFR-2)、缺血诱导因子-1α(HIF-1α)mRNA的表达水平。结果与模型组比较,邓老冠心方高低剂量组及辛伐他汀组对CD34阳性染色的新生血管含量均较模型组减少(P <0.05),大剂量组、辛伐他汀组与小剂量组比较有统计学意义(P <0.05)。与正常对照组比较,模型组小鼠血管壁VEGF、VEGFR2-2、HIF-1α mRNA表达水平明显升高(P <0.001);各药物处理组和模型组相比较表达均显著下降(P <0.01),其中高剂量组下降最明显与辛伐他汀组及低剂量组比较有统计学意义(P <0.05)。结论邓老冠心方可抑制Apo E-/-小鼠AS斑块内的血管新生,并具有剂量依赖性,其机制可能与影响斑块内VEGF、VEGFR-2、HIF-1α mRNA的表达有关。

Objective To explore the possible mechanism of Denglao Guanxin（DG） formula on the formation and rupture of unstable plaque of atherosclerosis（AS）. Methods A total of male ApoE-/-mice were fed with highfat diet for 13 weeks to induce atherosclerosis（AS）. And then the modeled mice were randomly divided into model group, high-dose DG, low-dose DG group, simvastatin group. Distilled water, DG formula and simvastatin were given to the corresponding groups following the experimental design for another successive 12 weeks. Through histopathological analysis sections were stained, the expressions of（CD）34 were detected. The expression of vascular endothelial growth factor（VEGF）, receptor 2（VEGFR2） and ischemic inducible factor-1α（HIF-1α）m RNA were measured. Results Compared with the model group, CD34-positive staining neovascularization reduced to varying sianificant degrees in high-dose DG, low-dose DG group, simvastatin group（P〈0.05）. There was a significant difference of high-dose DG, Simvastatin group compared with low-dose DG group（P〈0.05）. The expressions of VEGF, VEGFR2, HIF-1αm RNA in the model group were higher than that in the normal group（P〈0.001）. After treatment the expressions of VEGF, VEGFR2, HIF-1αmRNA were decreased in a different degree compared with the model group（P〈0.01）. Among those treatment groups, high-dose DG group decreased in the most significant degree,and there was a significant difference of those two groups compared with Simvastatin and low-dose DG group（P〈0.05）. Conclusion Denglao Guanxin Formula could inhibit plaque angiogesis. The mechanisms were possibly associated with the suppressive effect of VEGF, VEGFR2, HIF-1α m RNA expression in aortas of ApoE-/-mice with Atherosclerosis.