Polydatin inhibits the oxidative stress-induced proliferation of vascular smooth muscle cells by activating the eNOS/SIRT1 pathway
Polydatin inhibits the oxidative stress-induced proliferation of vascular smooth muscle cells by activating the eNOS/SIRT1 pathway
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DOI：
10.3892/ijmm.2016.2554
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发表时间：
2016-06-01
影响因子：
5.4
通讯作者：
Wu, Saizhu
中科院分区：
文献类型：
--
作者：
Ma, Yi;Gong, Xun;Wu, Saizhu
氧化应激介导的血管平滑肌细胞（VSMC）增殖有助于斑块形成和动脉粥样硬化的进展。虎杖甙是白藜芦醇的衍生物，广泛存在于某些用于治疗心血管疾病的草药中。在本研究中，我们检查了虎杖甙是否能够减弱氧化应激诱导的 VSMC 增殖以及内皮一氧化氮合成酶 (eNOS)/SIRT1 通路的潜在参与。简而言之，在进行细胞增殖测定之前，在不存在或存在虎杖甙（10-100μM）的情况下，将VSMC暴露于H2O2中24小时。在机制研究中，在虎杖甙处理之前，将细胞与沉默信息调节因子 1 (SIRT1) 抑制剂 EX527 或 eNOS 抑制剂 L-NAME 一起孵育。结果显示，虎杖甙可抑制VSMC增殖和活性氧水平，增加Kip1/p27、SIRT1和eNOS的表达，而降低cyclin B1、Cdk1和c-myc的表达。 G2/M期细胞数量增加。 L-NAME预处理减弱了虎杖甙对细胞增殖的抑制作用，抑制了SIRT1的表达和eNOS的磷酸化。 EX527预处理也减弱了虎杖甙对细胞增殖的抑制作用，但未能减少eNOS的激活和一氧化氮的产生。综上所述，这些研究结果表明，虎杖甙通过激活 eNOS/SIRT1 途径抑制氧化应激诱导的 VMSC 增殖。
Oxidative stress-mediated proliferation of vascular smooth muscle cells (VSMCs) contributes to plaque formation and the progression of atherosclerosis. Polydatin is a derivative of resveratrol, and is widely present in certain herbal medications used for the treatment of cardiovascular diseases. In the present study, we examined whether polydatin was capable of attenuating VSMC proliferation induced by oxidative stress as well as the potential involvement of the endothelial nitric oxide synthetase (eNOS)/SIRT1 pathway. Briefly, VSMCs were exposed to H2O2 for 24 h in the absence or presence of polydatin (10-100 mu M) prior to performing a cell proliferation assay. In mechanistic studies, the cells were incubated with the silent information regulator 1 (SIRT1) inhibitor, EX527, or the eNOS inhibitor, L-NAME, prior to polydatin treatment. The results showed that polydatin inhibited VSMC proliferation and the level of reactive oxygen species, increased the expression of Kip1/p27, SIRT1 and eNOS, whereas the expression of cyclin B1, Cdk1 and c-myc was decreased. The number of cells in the G2/M phase was increased. Pre-treatment with L-NAME attenuated the inhibitory effects of polydatin on cell proliferation, inhibited the expression of SIRT1 and the phosphorylation of eNOS. Pre-treatment with EX527 also attenuated the inhibitory effects of polydatin on cell proliferation, but failed to reduce the activation of eNOS and the production of nitric oxide. Taken together, these findings suggest that, polydatin inhibited the oxidative stress-induced proliferation of VMSCs by activating the eNOS/SIRT1 pathway.