芪参益气滴丸抗血管新生大鼠心肌缺血动态观察及机制探讨  

Dynamic Observation and Mechanism of Qishen Yiqi Drop Pills on Myocardial Ischemia in Rats Based on Angiogenesis

作　　者：张腾[1] 张密霞[1] 张艳军[1] 

机构地区：[1]天津中医药大学,天津300193

出　　处：《中国实验方剂学杂志》2017年第1期134-139,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81202943)

摘　　要：目的:基于血管新生,探讨芪参益气滴丸对心肌缺血大鼠心肌损伤的保护作用及机制。方法:160只远交群SD大鼠分为假手术组、模型组、芪参益气滴丸高、低剂量组,结扎冠状动脉左前降支复制大鼠心肌缺血模型,术后3,7,14,28 d苏木素伊红(HE)染色检测心脏病理学变化,免疫组织化学染色检测缺血边缘区血管密度,血小板-内皮细胞黏附分子(platelet endothelial cell adhesion molecule-1,PECAM-1/CD31),α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA),实时荧光定量PCR法检测边缘区血管新生及成熟相关基因血管内皮生长因子(vascular endothelial growth factor,VEGF),血管内皮生长因子受体2(vascular endothelial growth factor receptor 2,KDR),碱性成纤维细胞生长因子(basic fibroblast growth factor,b FGF),血小板源性生长因子-B(plateletderived growth factor-B,PDGF-B),血小板源性生长因子受体-β(plateletderived growth factor receptor beta,PDGFR-β),血管生成素1(angiopoietin-1,Ang-1),血管生成素2(angiopoietin-2,Ang-2)信使核糖核酸(messenger RNA,mRNA)的表达。结果:大鼠心肌梗死后3 d心脏可见明显梗死区,7~28 d左心室扩张,梗死区室壁变薄,3~28 d梗死边缘区均可见新生毛细血管,CD31阳性及α-SMA阳性血管密度较假手术增加。与模型组比较,芪参益气滴丸高低剂量组各时间点可减小心肌梗死面积,促进边缘区血管新生,7~28 d可抑制心室扩张(P<0.05)。PCR结果显示心肌梗死早期血管新生及稳定相关因子均升高,后期新生因子表达降低,血管成熟相关因子升高(P<0.05)。芪参益气滴丸给药3 d能促进VEGF,Ang-1 mRNA表达,降低b FGF mRNA表达(P<0.05);7 d能促进VEGF,b FGF mRNA表达(P<0.05),14 d能促进VEGF,Ang-1,b FGF,PDGFR-βmRNA表达(P<0.05);28 d能促进b FGF mRNA表达(P<0.05),降低VEGF,KDR,Ang-1,Ang-2 mRNA表达(P<0.05)。结论:芪参益气滴丸能保护心肌缺血大鼠缺血心肌,减小心肌梗死面积,抑制左心室扩张,其机制与调Objective： To investigate the protective effect and mechanism of Qishen Yiqi drop pills on myocardial injury in rats with myocardial ischemia based on angiogenesis theory. Method： The 160 Sprague Dawley（SD） rats were divided into sham operation group,model group,high dose Qishen Yiqi drop pills group,and low dose Qishen Yiqi drop pills group. Myocardial ischemia models were established by ligating left anterior descending coronary artery in rats. Hematoxylin-eosin（HE） staining was used to detect cardiac pathological changes,platelet endothelial cell adhesion molecule-1（PECAM-1/CD31）,and α-smooth muscle actin（α-SMA）on days 3,7,14 and 28,immunohistochemical staining was used to detect the blood vessel density in ischemic border zone. Real-time PCR method was used to detect the expression levels of vascular endothelial growth factor（VEGF）,vascular endothelial growth factor receptor 2（KDR）,basic fibroblast growth factor（b FGF）,angiopoietin（Ang）-1,Ang-2 and platelet derived growth factor-B（PDGF-B） and platelet derived growth factor receptor-beta（PDGFR-β） mRNA. Result： After 3 days of infarction,the infarction area was obviously seen in heart,on days 7 ～ 28,with left ventricular dilation,the infarct zone wall was thinning; on days 3 ～ 28,new blood capillaries were seen in ischemic border zone; CD31 positive and α-SMA positive blood vessel densities were increased than those in sham operation group. As compared with the model group,high and low dose Qishen Yiqi drop pills could decrease the myocardial infarct size and promote the blood vessels in the border zone at different time points,and could inhibit ventricular dilatation at days 7 ～ 28（P〈0. 05）. PCR results showed that in the early stage of miocardial infarction,angiogenesis and stability related factors were increased; in the late stage of miocardial infarction,vascular maturation related factors were increased（P〈0. 05）. On day 3 of Qishen Yiqi drop pills treatment,the expression levels of VEGF a

关 键 词：芪参益气滴丸 心肌缺血 血管新生 Α-平滑肌肌动蛋白 血管内生长因子 血管生成素 

分 类 号：R285.5[医药卫生—中药学]