Liu Ya, Hao Fei, Zhang Haigang, Cao Dayan, Lu Xiaolan, Li Xiaohui
Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, China.
Cell Physiol Biochem. 2013;32(4):814-26. doi: 10.1159/000354484. Epub 2013 Sep 20.
Endothelial progenitor cells (EPCs) derived from the bone marrow (BM) play a key role in the homeostasis of vascular repair by enhanced reendothelialization. Panax notoginseng saponins (PNS), a highly valued traditional Chinese medicine, has been shown to reduce morbidity and mortality from coronary artery disease. The present research was designed to explore the contribution of progenitor cells to the progression of atherosclerotic plaques and the possible modulatory role of PNS in this process.
PNS (60 or 120 mg/kg via intraperitoneal injection) was administered over 8 weeks in apolipoprotein E knockout mice on an atherogenic diet. The sizes and histochemical alteration of atherosclerotic lesions and numbers of EPCs in BM and peripheral blood were analyzed. The expression of chemokine stromal cell-derived factor 1α (SDF-1α) and its receptor, CXCR4, was monitored as well.
PNS significantly reduced the lesion area and intima-to-media ratio compared to vehicle treatment. PNS also augmented endothelialization and reduced the smooth muscle cell (SMCs) content of the lesions. The number of c-kit and sca-1 double-positive progenitor cells and flk-1 and sca-1 double-positive progenitor cells were significantly increased in the BM and the peripheral blood of the PNS-treated groups. PNS treatment increased the plasma levels of SDF-1α and SCF as well as the BM levels of matrix metalloproteinase-9 (MMP-9). Moreover, the mRNA levels of SDF-1α and protein levels of CXCR4 were both increased in the BM of mice treated with PNS, while SDF-1α expression decreased.
PNS reduce the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilization. SDF-1α-CXCR4 interactions and the possible modulatory role of PNS in this process may contribute to the increased progenitor cell mobilization.
源自骨髓的内皮祖细胞（EPCs）通过增强再内皮化在血管修复的稳态中发挥关键作用。三七总皂苷（PNS）是一种备受重视的传统中药，已显示可降低冠状动脉疾病的发病率和死亡率。本研究旨在探讨祖细胞对动脉粥样硬化斑块进展的作用以及PNS在此过程中可能的调节作用。
在给予致动脉粥样硬化饮食的载脂蛋白E基因敲除小鼠中，腹腔注射PNS（60或120mg/kg），持续8周。分析动脉粥样硬化病变的大小和组织化学改变以及骨髓和外周血中EPCs的数量。同时监测趋化因子基质细胞衍生因子1α（SDF-1α）及其受体CXCR4的表达。
与溶剂处理相比，PNS显著减小了病变面积和内膜中膜比。PNS还增强了内皮化并减少了病变中的平滑肌细胞（SMC）含量。PNS处理组的骨髓和外周血中c-kit和sca-1双阳性祖细胞以及flk-1和sca-1双阳性祖细胞的数量显著增加。PNS处理增加了血浆SDF-1α和SCF水平以及骨髓基质金属蛋白酶-9（MMP-9）水平。此外，PNS处理小鼠的骨髓中SDF-1α的mRNA水平和CXCR4的蛋白水平均升高，而SDF-1α表达降低。
PNS减小了动脉粥样硬化斑块的大小，这种作用似乎涉及祖细胞的动员。SDF-1α-CXCR4相互作用以及PNS在此过程中可能的调节作用可能有助于增加祖细胞的动员。
