Farrokhi Effat, Ghatreh-Samani Keihan, Salehi-Vanani Najmeh, Mahmoodi Amin
Assistant Professor, Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Associate Professor, Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
ARYA Atheroscler. 2018 Jul;14(4):157-162. doi: 10.22122/arya.v14i4.1484.
Matrix metalloproteinase 9 (MMP-9) is involved in extracellular matrix degradation and remodeling. An increase in MMP-9 expression by vascular component cells plays an important role in atherosclerotic plaque formation and rupture. Resveratrol, a polyphenolic substance, was suggested to play a role in preventing the progress of atherosclerotic disease. The aim of this study was to investigate the effect of resveratrol on MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) in vascular smooth muscle cells (VSMCs) after treatment with H2O2.
Cultured VSMCs were pre-treated with 0.2 mM of H2O2 before stimulation with different concentration of resveratrol. Expression of MMP-9, TIMP-1, and TIMP-3 genes were measured using real-time polymerase chain reaction (PCR) method, and MMP-9 protein level was detected using western blot analysis.
Resveratrol at 120 μmol/l concentration reduced the elevated level of MMP-9 induced by H2O2 in VSMCs as 1.85 ± 0.35 folds (P < 0.050) and 8.70 ± 1.20 folds (P < 0.050) after 24 and 48 hours, respectively. Resveratrol increased the diminished level of TIMP-1 induced by H2O2 as 2.5 ± 0.48 folds following the treatment with 120 μmol/l after 48 hours (P < 0.050).
Resveratrol as an antioxidant can decrease MMP-9 production, not only by suppressing MMP-9 expression, but also by augmenting TIMP-1 production. Altogether, resveratrol as an antioxidant can regulate the MMP-9/TIMP-1 balance, and may be considered as a preservative agent in the treatment and prevention of atherosclerosis.
基质金属蛋白酶9（MMP - 9）参与细胞外基质的降解和重塑。血管成分细胞中MMP - 9表达的增加在动脉粥样硬化斑块形成和破裂中起重要作用。白藜芦醇是一种多酚类物质，被认为在预防动脉粥样硬化疾病进展中发挥作用。本研究的目的是探讨白藜芦醇对过氧化氢处理后血管平滑肌细胞（VSMC）中MMP - 9和金属蛋白酶组织抑制剂（TIMP）的影响。
培养的VSMC在用不同浓度的白藜芦醇刺激前先用0.2 mM的过氧化氢预处理。使用实时聚合酶链反应（PCR）方法检测MMP - 9、TIMP - 1和TIMP - 3基因的表达，并使用蛋白质印迹分析检测MMP - 9蛋白水平。
浓度为120 μmol/l的白藜芦醇在24小时和48小时后分别将过氧化氢诱导的VSMC中升高的MMP - 9水平降低了1.85±0.35倍（P < 0.050）和8.70±1.20倍（P < 0.050）。在用120 μmol/l处理48小时后，白藜芦醇使过氧化氢诱导降低的TIMP - 1水平增加了2.5±0.48倍（P < 0.050）。
白藜芦醇作为一种抗氧化剂可以降低MMP - 9的产生，不仅通过抑制MMP - 9的表达，还通过增加TIMP - 1的产生。总之，白藜芦醇作为一种抗氧化剂可以调节MMP - 9/TIMP - 1平衡，并且在动脉粥样硬化的治疗和预防中可被视为一种保护剂。
