黄芪丹参配伍提取物对心肌缺血大鼠的心脏保护作用

为证实黄芪丹参配伍提取物对心肌缺血模型大鼠的心脏具有保护作用，通过左前降支结扎诱导心肌梗死（MI）大鼠模型的方法，研究培哚普利组（PB组）、黄芪组（HQ组）、丹参组（DS组）、黄芪丹参配伍提取物组（HQ+DS组）等药物干预后对心功能的影响。采用Notch信号抑制剂RO4929097探讨Notch信号在HQ+DS组诱导心肌梗死边缘区（infarcted border zone，IBZ）血管生成中的作用。用动物超声和Masson染色评价左室射血分数（left ventricular ejection fraction，LVEF）和心肌梗死面积百分比。用免疫荧光法测定心肌IBZ中CD31和vWF的平均光密度（average optical densities，AODs）。Western blot法检测低氧诱导因子1-??（hypoxia inducible factor 1-alpha，HIF-1??）、成纤维细胞生长因子受体1（fibroblast growth factor receptor 1，FGFR-1）、Notch1和Notch胞内结构域（Notch intracellular domain，NICD）等血管生成相关蛋白和干细胞动员相关蛋白，例如基质细胞衍生因子1（stromal cell-derived factor 1，SDF-1）、C-X-C趋化因子受体4型（C-X-C chemokine receptor type 4，CXCR-4）和心肌营养素1（cardiotrophin 1，CT-1）。结果表明：与模型组相比，治疗3周后HQ+DS和PB组的LVEF均明显改善、心肌梗死面积降低，尽管与模型组相比HQ组和DS组LVEF增加、心肌梗死面积减少，但差异不显著；模型组和HQ+DS-I组IBZ中CD31的AODs均明显低于假手术组，与模型组相比，HQ+DS显著增加IBZ中CD31的 AODs，降低梗死区CD31和vWF的AODs；模型组和各治疗组HIF-1的表达均高于假手术组；与模型组相比，HQ+DS组的FGFR-1、SDF-1、CT-1、Notch1和NICD表达增加；与HQ+DS组相比，HQ+DS-I组的Notch1和NICD表达降低。可见黄芪丹参配伍对IBZ心肌细胞的保护作用优于黄芪或丹参单独应用，黄芪丹参配伍保护MI大鼠的的机制可能通过Notch信号传导和动员干细胞向IBZ移动而发挥促血管新生作用。

Cardioprotective Effects of Compatible Extracts of Astragalus Membranaceus and Salvia Miltiorrhiza on Myocardial Ischemia Rats

In order to confirm the protective effect of compatible extracts of Radix Astragali and Salvia Miltiorrhiza on the heart of rats with myocardial ischemia, the effects of perindopril group (PB group), Radix Astragali group (HQ group), Radix Salviae Miltiorrhizae group (DS group), Radix Astragali and Salvia Miltiorrhizae compatible extracts group (HQ + DS group) on cardiac function were studied by ligating left anterior descending branch to induce myocardial infarction (MI Notch signal inhibitor RO4929097 was used to investigate the role of Notch signal in inducing angiogenesis in the infarcted border zone (IBZ) of myocardial infarction in HQ + DS group. The left ventricular ejection fraction (LVEF) and the percentage of myocardial infarction area were evaluated by echocardiography and Mason staining. The average optical densities (AODs) of CD31 and vWF in myocardial IBZ were measured by immunofluorescence. Western blot was used to detect angiogenesis-related proteins such as hypoxia inducible factor 1-alpha (HIF-1), fibroblast growth factor receptor 1 (fibroblast growth factor receptor 1, FGFR-1), Notch 1 and Notch intracellular domain (NICD) and stem cell mobilization-related proteins, such as stromal cell derived factor 1 (stromal cell derived factor 1). Ll-derived factor 1 (SDF-1), C-X-C chemokine receptor type 4 (CXCR-4) and cardiotrophin 1 (CT-1). The results showed that compared with the model group, the LVEF of HQ+DS and PB groups improved significantly and the infarct area decreased after 3 weeks of treatment, although the LVEF of HQ group and DS group increased and the infarct area decreased, but the difference was not significant. The AODS of CD31 in IBZ of model group and HQ+DS-I group were significantly lower than that of sham operation group. Compared with model group, HQ+DS group increased significantly the AODS of CD31 in IBZ and decreased the infarct area. AODs of CD31 and vWF in dead zone; expression of HIF-1 in model group and each treatment group was higher than that in sham operation group; expression of fibroblast growth factor R-1, SDF-1, CT-1, Notch 1 and NICD in HQ+DS group was higher than that in model group; expression of Notch1 and NICD in HQ+DS-I group was lower than that in HQ+DS group. It is concluded that the protective effect of compatibility of Astragalus and Salvia miltiorrhiza on IBZ myocardial cells is better than that of Astragalus or Salvia miltiorrhiza alone. The mechanism of compatibility of Astragalus and Salvia miltiorrhiza in protecting MI rats may play a role in promoting angiogenesis through Notch signal transduction and mobilization of stem cells to IBZ.