Zhang Jing, Chen Jing, Yang Jian, Xu Chang-Wu, Pu Peng, Ding Jia-Wang, Jiang Hong
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, PR China.
Cell Physiol Biochem. 2013;31(2-3):230-41. doi: 10.1159/000343364. Epub 2013 Feb 14.
BACKGROUND/AIM: Oxidative stress plays a critical role in pathogenesis of the neointimal arterial hyperplasia. The aim of the study was to evaluate effects of resveratrol (RSV) on the vascular hyperplasia stimulated by oxidative damage.
Balloon vascular injury was induced in rats that were intraperitonealy exposed to resveratrol (1 mg/kg) on 7 or 14 days after surgical procedure. Animals were euthanized on 7 or 14 days after operation. The blood level of 8-iso-prostaglandin F2α, arterial morphology as well as expression of monocyte chemotactic protein-1 and interleukin-6 in carotid wall were measured. Vascular smooth muscle cells (VSMCs) were isolated from the thoracic aorta. Cellular proliferation and migration assays, reactive oxygen species (ROS), superoxide dismutase (SOD) and NADPH oxidative activity, protein level of β-actin, histone H3, NF-ĸB p65, IĸB, ERK1/2, phospho-ERK1/2, phospho-p38 as well as NF-ĸB transcription activity were evaluated in-vitro after angiotensin II stimulation and resveratrol (50-200 µmol/L) treatment.
Significant decreases in neointimal/medial area, serum prostaglandin level and genes expression were found in rats treated with resveratrol, when compared to the control group. Significant changes were also revealed for proliferation and migration rates, ROS level, as well as SOD, NADPH oxidase, ERK1/2 phosphorylation and NF-ĸB transcriptional activity in cell cultures exposed to highest dose of resveratrol. Insignificant changes were observed for NF-kappaB p65 translocation and IĸB degradation, p38 phosphorylation in MAPK pathway.
Resveratrol significantly suppressed the neointimal hyperplasia after balloon injury through inhibition of oxidative stress and inflammation by blocking the ERK1/2/NF-kappa B pathway.
背景/目的：氧化应激在新生内膜动脉增生的发病机制中起关键作用。本研究旨在评估白藜芦醇（RSV）对氧化损伤刺激的血管增生的影响。
在手术操作后7天或14天，对腹腔注射白藜芦醇（1 mg/kg）的大鼠进行球囊血管损伤。术后7天或14天对动物实施安乐死。检测8-异前列腺素F2α的血液水平、动脉形态以及颈动脉壁中单核细胞趋化蛋白-1和白细胞介素-6的表达。从胸主动脉分离血管平滑肌细胞（VSMC）。在血管紧张素II刺激和白藜芦醇（50 - 200 µmol/L）处理后，体外评估细胞增殖和迁移试验、活性氧（ROS）、超氧化物歧化酶（SOD）和NADPH氧化活性、β-肌动蛋白、组蛋白H3、NF-κB p65、IκB、ERK1/2、磷酸化ERK1/2、磷酸化p38的蛋白水平以及NF-κB转录活性。
与对照组相比，白藜芦醇处理的大鼠新生内膜/中膜面积、血清前列腺素水平和基因表达显著降低。在暴露于最高剂量白藜芦醇的细胞培养物中，增殖和迁移率、ROS水平以及SOD、NADPH氧化酶、ERK1/2磷酸化和NF-κB转录活性也有显著变化。在MAPK途径中，未观察到NF-κB p65易位和IκB降解、p38磷酸化的显著变化。
白藜芦醇通过阻断ERK1/2/NF-κB途径抑制氧化应激和炎症，显著抑制球囊损伤后的新生内膜增生。
