Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University, Jinan, Shandong, China.
PLoS One. 2013;8(1):e54303. doi: 10.1371/journal.pone.0054303. Epub 2013 Jan 18.
Endothelial progenitor cells (EPCs) can be used to repair tissues after myocardial infarction (MI) but EPC activators have adverse reactions. Rehmannia glutinosa is a herb used in traditional Chinese medicine, which can promote bone-marrow proliferation and protect the ischemic myocardium. We investigated the effects of Rehmannia glutinosa extract (RGE) on EPCs in a rat model of MI.
A total of 120 male Wistar rats were randomized to 2 groups (n=60 each) for treatment: high-dose RGE (1.5 g·kg(-1)·day(-1) orally) for 8 weeks, then left anterior descending coronary artery ligation, mock surgery or no treatment, then RGE orally for 4 weeks; or normal saline (NS) as the above protocol. The infarct region of the left ventricle was assessed by serial sectioning and morphology. EPCs were evaluated by number and function. Protein and mRNA levels of CD133, vascular endothelial growth factor receptor 2 (VEGFR2), chemokine C-X-C motif receptor 4 (CXCR4), stromal cell-derived factor-1α (SDF-1α) were measured by immunohistochemistry, Western blot and quantitative PCR analysis.
RGE significantly improved left ventricular function, decreased the ischemic area and the apoptotic index in the infarct myocardium, also decreased the concentration of serum cardiac troponin T and brain natriuretic peptide at the chronic stage after MI (from week 2 to week 4). RGE increased EPC number, proliferation, migration and tube-formation capacity. It was able to up-regulate the expression of angiogenesis-associated ligand/receptor, including CD133, VEGFR2 and SDF-1α/CXCR4. In vitro, the effect of RGE on SDF-1α/CXCR4 cascade was reversed by the CXCR4 specific antagonist AMD3100.
RGE may enhance the mobilization, migration and therapeutic angiogenesis of EPCs after MI by activating the SDF-1α/CXCR4 cascade.
内皮祖细胞（EPCs）可用于修复心肌梗死后的组织损伤，但 EPC 激活剂有不良反应。地黄是一种中药，能促进骨髓增殖，保护缺血心肌。我们研究了地黄提取物（RGE）对心肌梗死大鼠模型中 EPC 的作用。
120 只雄性 Wistar 大鼠随机分为 2 组（每组 60 只）：RGE 高剂量组（1.5 g·kg(-1)·d(-1) 口服）治疗 8 周，然后结扎左前降支冠状动脉，假手术或不治疗，然后 RGE 口服 4 周；或生理盐水（NS）作为上述方案。通过连续切片和形态学评估左心室梗死区。通过数量和功能评估 EPC。用免疫组化、Western blot 和定量 PCR 分析检测 CD133、血管内皮生长因子受体 2（VEGFR2）、趋化因子 C-X-C 基序受体 4（CXCR4）、基质细胞衍生因子-1α（SDF-1α）的蛋白和 mRNA 水平。
RGE 显著改善左心室功能，减少梗死心肌的缺血区和细胞凋亡指数，也降低慢性期心肌梗死后血清心肌肌钙蛋白 T 和脑钠肽的浓度（从第 2 周到第 4 周）。RGE 增加 EPC 数量、增殖、迁移和管状形成能力。它能够上调血管生成相关配体/受体的表达，包括 CD133、VEGFR2 和 SDF-1α/CXCR4。在体外，RGE 对 SDF-1α/CXCR4 级联的作用被 CXCR4 特异性拮抗剂 AMD3100 逆转。
RGE 可能通过激活 SDF-1α/CXCR4 级联来增强心肌梗死后 EPC 的动员、迁移和治疗性血管生成。
