The Effect Of2,3,4’,5-tetrahydroxystilbene-2-0-β-D Glucoside On Neointima Formation In A Rat Artery Balloon Injury Model And Its Possible Mechanisms

Objective In order to detect if2,3,4’,5-tetrahydroxystilbene-2-0-β-D glucoside (TSG) has effects on VSMCs proliferation and migration, we designed to investigate the underlying mechanism in carotid artery of rats after balloon injury.Methods In vivo:Fifty-six healthy male Sprague-Dawley rats were randomly divided into seven groups:a control group (n=8), a model group (n=8), a positive-control group (Simvastatin,2mg·kg-1·d-1, n=8), a sham-operation group (n=8), and three TSG-treated (30/60/120mg·kg-1·d-1, n=8) groups, treated with TSG3days before balloon injury until the end of the experiment. Fourteen days after balloon injured, rats were sacrificed, the serum and carotid arterys were collected for morphology observation and key proteins or genes detection; In vitro:Rat VSMCs were obtained from thoracic aorta of Sprague-Dawley rats, and cultured by tissue explants method. VSMCs between passages4and8were used in this experiment. The effect of TSG on VSMCs migration was measured with a wound healing assay and modified Boyden’s chamber method, and some key proteins or genes detection. Results Hematoxylin-eosin staining showed that TSG significantly reduced the neointimal areas in TSG (120mg·kg-1·d-1) group14days after balloon injury. Immunohistochemical analysis showed that PCNA and α-SMA expressions in the neointima were significantly decreased in TSG (120mg·kg-1·d-1) group. Biochemical indicator in blood serum explored that TSG significantly up-regulated the levels of No, c-GMP, SOD and down-regulated the level of PDGF-BB, MDA. Western blot and RT-PCR analysis showed that TSG inhibits rVSMCs proliferation may through blocking ERK1/2and AKT signal pathways. We also investigated the effect of TSG on PDGF-BB-induced rat VSMCs migration, and our data implied that TSG inhibits rVSMCs migration may be via blocking MMP-2and MMP-9expressions. And in both vivo and vitro model, TSG markedly regulated matrix metalloproteinase-2,-9expressions and collagen I, III expressions, which are key factors in extracellular matrix for VSMCs migration.Conclusions1. TSG significantly improved neointima formation following balloon injury at a rat carotid artery.2. TSG can significantly inhibited vascular smooth muscle cells (VSMCs) proliferation and migration.3. The underlying mechanisms of inhibition of TSG on atherosclerosis may via blocking ERK1/2and AKT signaling pathways, NF-κB regulatory system and MMPs activation.