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Abstract：
BACKGROUND: Intimal hyperplasia is the major therapeutic concern after percutaneous coronary intervention. The aim of this study is to investigate effects of 2,3,4\',5-tetrahydroxystilbene-2-O-β-D glucoside (TSG) on intimal hyperplasia and the underling mechanisms through attenuating the expressions of stromal cell-derived factor-1α (SDF-1α)/CXCR4, stem cell factor (SCF)/c-kit and fractalkine (FKN)/CX3CR1, and through promoting re-endothelialization with vascular endothelial growth factor (VEGF).
METHODS: Rats were operated with carotid artery balloon injury. The treatment groups were gavaged with 50 and 100 mg/kg/d of TSG. After 10 days of treatment, carotid artery pathological changes were evaluated by histology. Serum levels of SDF-1α, SCF, FKN and VEGF were detected by enzyme linked immunosorbent assay. The protein expressions of the receptors c-kit, CXCR4, CX3CR1, as well as CD34 and proliferating cell nuclear antigen (PCNA) were detected by immunochemistry.
RESULTS: TSG dose-dependently inhibited balloon injury-induced intimal hyperplasia, as evidenced by reducing neointima area (NIA), neointima area/media area (NIA/MA), neointima area/internal elastic area (NIA/IELA), and by decreasing the protein expression of PCNA. TSG reduced serum levels of SDF-1α, SCF and FKN, and it also decreased the expressions of the corresponding receptors c-kit, CXCR4, CX3CR1 in neointima. Importantly, the level of VEGF in peripheral blood and the expression of CD34 in vascular walls were increased to promote re-endothelialization.
CONCLUSIONS: This study clearly demonstrated that TSG was effective in inhibiting intimal hyperplasia, and this effect was mediated, at least in part, through the SCF/c-kit, SDF-1α/CXCR4 and FKN/CX3CR1 axes. Importantly, TSG could increase VEGF and CD34 to promote endothelial repair.
METHODS: Rats were operated with carotid artery balloon injury. The treatment groups were gavaged with 50 and 100 mg/kg/d of TSG. After 10 days of treatment, carotid artery pathological changes were evaluated by histology. Serum levels of SDF-1α, SCF, FKN and VEGF were detected by enzyme linked immunosorbent assay. The protein expressions of the receptors c-kit, CXCR4, CX3CR1, as well as CD34 and proliferating cell nuclear antigen (PCNA) were detected by immunochemistry.
RESULTS: TSG dose-dependently inhibited balloon injury-induced intimal hyperplasia, as evidenced by reducing neointima area (NIA), neointima area/media area (NIA/MA), neointima area/internal elastic area (NIA/IELA), and by decreasing the protein expression of PCNA. TSG reduced serum levels of SDF-1α, SCF and FKN, and it also decreased the expressions of the corresponding receptors c-kit, CXCR4, CX3CR1 in neointima. Importantly, the level of VEGF in peripheral blood and the expression of CD34 in vascular walls were increased to promote re-endothelialization.
CONCLUSIONS: This study clearly demonstrated that TSG was effective in inhibiting intimal hyperplasia, and this effect was mediated, at least in part, through the SCF/c-kit, SDF-1α/CXCR4 and FKN/CX3CR1 axes. Importantly, TSG could increase VEGF and CD34 to promote endothelial repair.
摘要：
背景：内膜增生是经皮冠状动脉介入治疗后的主要治疗问题。这项研究的目的是调查2,3,4'，5-四羟基二苯乙烯-2-O-β-D葡萄糖苷（TSG）通过抑制基质细胞衍生因子-1α（SDF-1α）/CXCR4，干细胞因子（SCF）/c-kit和Fractalkine（FKN）/CX3CR1的表达，并通过促进血管内皮生长因子（VEGF）的再内皮内皮化。
方法：大鼠行颈动脉球囊损伤手术。治疗组分别用50和100mg/kg/d的TSG进行灌洗。治疗10天后，通过组织学评估颈动脉病理变化。血清SDF-1α水平,SCF,酶联免疫吸附法检测FKN和VEGF。受体c-kit的蛋白表达，通过免疫化学检测CXCR4，CX3CR1以及CD34和增殖细胞核抗原（PCNA）。
结果：TSG剂量依赖性地抑制球囊损伤引起的内膜增生，如减少新内膜面积（NIA）所证明的，新内膜面积/中膜面积（NIA/MA），新内膜面积/内部弹性面积（NIA/IELA），并通过降低PCNA的蛋白表达。TSG降低血清SDF-1α水平，SCF和FKN,它也降低了相应受体c-kit的表达，新内膜中CXCR4、CX3CR1。重要的是,外周血中VEGF水平和血管壁中CD34的表达增加以促进再内皮化。
结论：这项研究清楚地表明，TSG可有效抑制内膜增生，这种效应是介导的，至少在某种程度上,通过SCF/C-Kit，SDF-1α/CXCR4和FKN/CX3CR1轴。重要的是,TSG可增加VEGF和CD34促进内皮修复。
方法：大鼠行颈动脉球囊损伤手术。治疗组分别用50和100mg/kg/d的TSG进行灌洗。治疗10天后，通过组织学评估颈动脉病理变化。血清SDF-1α水平,SCF,酶联免疫吸附法检测FKN和VEGF。受体c-kit的蛋白表达，通过免疫化学检测CXCR4，CX3CR1以及CD34和增殖细胞核抗原（PCNA）。
结果：TSG剂量依赖性地抑制球囊损伤引起的内膜增生，如减少新内膜面积（NIA）所证明的，新内膜面积/中膜面积（NIA/MA），新内膜面积/内部弹性面积（NIA/IELA），并通过降低PCNA的蛋白表达。TSG降低血清SDF-1α水平，SCF和FKN,它也降低了相应受体c-kit的表达，新内膜中CXCR4、CX3CR1。重要的是,外周血中VEGF水平和血管壁中CD34的表达增加以促进再内皮化。
结论：这项研究清楚地表明，TSG可有效抑制内膜增生，这种效应是介导的，至少在某种程度上,通过SCF/C-Kit，SDF-1α/CXCR4和FKN/CX3CR1轴。重要的是,TSG可增加VEGF和CD34促进内皮修复。
