黄芪甲苷Ⅳ对梗死小鼠心肌新生血管成熟及HIF-1α、VEGF蛋白表达的影响  

Effect of astragaloside Ⅳ on angiogenesis maturity in mice with myocardial infarction

作　　者：李军昌[1] 司静文[1,2] 刘海涛[3] 朱芳红[1] 王文[1] 马静[1] 王宗仁[1] 

机构地区：[1]第四军医大学西京医院中医科,陕西西安710032 [2]清华大学药学院,北京100084 [3]第四军医大学西京医院心脏内科,陕西西安710032

出　　处：《心脏杂志》2017年第3期269-275,共7页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(81072972);第四军医大学科技发展基金项目资助(2016XC215)

摘　　要：目的观察黄芪甲苷(Astragaloside,Astra)-Ⅳ对梗死小鼠心肌新生血管成熟及缺氧诱导因子(Hypoxia induced factor,HIF)-1α和血管内皮生长因子(Vascular endothelial cell factor,VEGF)蛋白表达的影响。方法结扎法制备小鼠心肌梗死(Myocardium Infarct,MI)模型,Astra-Ⅳ腹腔注射[2 mg/(kg·d)]21 d,通过小动物超声系统评价小鼠心功能;计算梗死面积(IS)与缺血区面积(AAR)的比值;CD31和α-SMA双荧光染色法观察梗死周边心肌组织新生和成熟血管密度;经鼠尾注射FITC-Lectin观察新生血管的灌注情况;Western blot检测MI区及其边缘组织HIF-1α、VEGF表达的变化。结果 Astra-Ⅳ可提高小鼠的FS(%)和EF(%)[(61.0±2.7)%vs.(40.2±3.9)%,P<0.05;(44.1±3.2)%vs.(29.1±4.1)%,P<0.05],减少MI范围[28.8±8.4)%vs.(45.1±9.3)%;P<0.05];MI+Astra-Ⅳ组心肌新生血管密度(214.0±21.3/mm^2),成熟血管密度(7.0±2.1/mm^2),有效灌注新生血管密度为(0.39±0.11)×10~5/pixels,与MI组比较均具有显著差异(P<0.01);MI+Astra-Ⅳ组显著增加周围组织的HIF-1α、VEGF蛋白水平(P<0.01)。结论 Astra-Ⅳ缩小MI面积,提高梗死心肌功能,并促进促血管新生和成熟,实现缺血组织有效灌注,其分子机制可能与HIF-1α和VEGF蛋白的表达增加有关。AIM To investigate the effect of astragaloside IV on angiogenesis maturity in mice with myo- cardial infarction （MI） and protein expression of hypoxia-induced factor lct and vascular endothelial cell factor. METHODS C57BL mice were randomly divided into three groups： sham, myocardial infarction （MI model） and astragaloside IV therapy （Astra-MI）. MI mice were established by permanent coronary artery ligation. Astragaloside IV （2 mg/kg/day ） was administrated intraperitoneally every day for 21 days. Left ventricular ejection fraction and fractional shortening were determined by Animal Visual Sonics System （Canada）. Areas at risk and infarct size were determined by Evans blue and tripheny] tetrazolium chloride （TTC） methods. CD31 and e-SMA fluorescent staining were used to observe the density of angiogenesis and maturity of vessels in the peri-infarction myoeardium tissue. Fusion angiogenesis density was determined by FITC-lectin fluorescent staining. Expressions of HIF-la and VEGF were determined by Western blot. RESULTS Left ventricular ejection fraction and fractional shortening were significantlyimproved in Astra-MI group, respectively, compared with those in MI model control [ （ 61.0 ± 2.7 ） % vs. （40. 2 ± 3.9 ） %, P 〈 0.05 ; （44. 1 ± 3.2 ） % vs. （29.1 ± 4. 1 ） %, P 〈 0. 05 ]. IS/AAR were signifi- cantly attenuated in Astra-MI group [ （28.8 ± 8.4） % vs. （45.1± 9.3 ） %, P 〈 0. 05 1. Angiogenesis density, vessel maturity and fusion angiogenesis in peri-infarction myocardium tissues in Astra-MI group were （214. 0 ± 21.3 ）/mini, （7.0 ± 2. 1 ）/ram2, and （0. 39 ±0. 11 ） x 104/pixels, respectively, which were all significantly better than those in the control group （P 〈0. 01 ）. Protein expressions of HIF-la and VEGF in the risk area of MI in Astra-MI group were higher than in controls （P 〈 0. 01 ）. CONCLUSION Astragaloside IV may reduce ischemia injury and improve function by improving effective angiogenesis density in mice with

关 键 词：黄芪甲苷Ⅳ HIF-1Α 血管新生 血管成熟 心肌梗死 

分 类 号：R285.5[医药卫生—中药学]