Velvet Antler Mobilizes Endothelial Progenitor Cells to Promote Angiogenesis and Repair Vascular Endothelial Injury in Rats Following Myocardial Infarction
Velvet Antler Mobilizes Endothelial Progenitor Cells to Promote Angiogenesis and Repair Vascular Endothelial Injury in Rats Following Myocardial Infarction
复制标题
鹿茸动员内皮祖细胞促进血管生成并修复心肌梗塞后大鼠血管内皮损伤
DOI：
10.3389/fphys.2018.01940
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发表时间：
2019-01-17
影响因子：
4
通讯作者：
Li, Lin
中科院分区：
文献类型：
--
作者：
Li, Yanjun;Wang, Ziwei;Li, Lin
目的：本研究探讨了鹿茸对心肌梗死（MI）大鼠内皮祖细胞（EPCs）的影响及其促进血管新生和修复血管内皮损伤的作用。方法：采用液相色谱-质谱联用技术对VA进行分析。将雄性Sprague道利大鼠随机分为4组：假手术组、MI组、VA组和VA + DAPT（γ-分泌酶抑制剂IX，Notch信号通路的特异性阻断剂）组。结扎大鼠冠状动脉左前降支建立心肌梗死模型。假手术大鼠作为对照。在术后第1天和第3天从眶丛采血，并在术后第7天将所有大鼠安乐死。检测外周血循环内皮祖细胞（CEPCs）和血管内皮生长因子（VEGF）的含量。超声心动图检查心功能。心肌组织用于免疫组织化学和电子显微镜，MI组织的边缘区用于western blot和逆转录-定量聚合酶链反应。结果：基本定性的代谢产物445个。其中，相对含量大于0.05%的物质有74种。VA可增加MI术后7 d血清CEPCs、VEGF浓度、CD 133含量和微血管密度（MVD），保护MI边缘区微血管内皮细胞形态。VA +DAPT组的CEPC和MVD低于VA组。VA可上调Jagged-1、Notch 1、NICD和HES 1的蛋白表达，上调Hes 1和Hey 2的mRNA表达，但部分作用可被DAPT抑制。结论：这些结果表明，VA促进动员EPCs，促进血管生成和修复血管内皮细胞损伤后，在MI大鼠，这些作用可能是由于激活的Notch信号通路。
Objective: This investigation examined the effect of velvet antler (VA) on endothelial progenitor cells (EPCs) and the associated effects to promote angiogenesis and repair vascular endothelial injury in rats with myocardial infarction (MI). Methods: VA was analyzed by liquid chromatography-mass spectrometry. Male Sprague Dawley rats were randomly divided into four groups: sham, MI, VA, and VA + DAPT (gamma-secretase inhibitor IX, a specific blocker of the Notch signaling pathway) group. The rats underwent ligation of the left anterior descending coronary artery for the establishment of MI. Sham-operated rats were used as controls. Blood was taken from the orbital plexus on the first and third days after the operation, and all rats were euthanized on the 7th day after surgery. The blood samples were used to detect the contents of circulating endothelial progenitor cells (CEPCs) and vascular endothelial growth factor (VEGF). Echocardiography was used to test the cardiac function. Cardiac tissue was used for immunohistochemistry and electron microscope, and the marginal zone of the MI tissue was used for western blot and reverse transcription-quantitative polymerase chain reaction. Results: The number of basically qualitative metabolites is 445. Among them, there are 74 substances with relative content greater than 0.05%. VA increased the concentration of CEPCs and VEGF in serum, CD133 content and microvessel density (MVD), and protected the morphology of microvascular endothelial cells in the marginal area of MI at 7 days post-MI surgery. CEPCs and MVD in the VA +DAPT group were lower than those of VA group. VA increased the protein expressions of Jagged-1, Notch1, NICD and HES1, and the mRNA expressions of Hes1 and Hey2, while some of the effects could be suppressed by DAPT. Conclusion: These results suggest that VA promotes the mobilization of EPCs to promote angiogenesis and repair vascular endothelial cell damage in post-MI rats, and these effects may be due to activation of the Notch signal pathway.