Xue Yun, Chen Huilian, Zhang Shenghao, Bao Li, Chen Beidong, Gong Huan, Zhao Yanyang, Qi Ruomei
MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China.
Graduate School of Peking Union Medical College, Beijing, China.
Oxid Med Cell Longev. 2021 Feb 25;2021:8819231. doi: 10.1155/2021/8819231. eCollection 2021.
This study investigated the effect of resveratrol on Toll-like receptor 4- (TLR4-) mediated matrix metalloproteinase 3 (MMP3) and MMP9 expression in oxidized low-density lipoprotein- (ox-LDL-) activated platelets and the potential molecule mechanism. Human platelets were used in the present study. The results showed that resveratrol suppressed TLR4, MMP3, and MMP9 expression in ox-LDL-activated platelets. The TLR4 inhibitor CLI-095 also inhibited MMP3 and MMP9 expression and secretion in ox-LDL- and lipopolysaccharide- (LPS-) activated platelets. The combination of resveratrol and CLI-095 synergistically suppressed MMP3 and MMP9 expression in ox-LDL- and LPS-activated platelets. These findings suggest that the resveratrol-induced inhibition of MMP3 and MMP9 expression is linked to the suppression of TLR4 activation. Resveratrol also suppressed spleen tyrosine kinase (Syk) phosphorylation and nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) expression and IL-1 secretion in ox-LDL- and LPS-treated platelets. The coimmunoprecipitation results showed that resveratrol inhibited the binding of Syk and NLRP3. Finally, resveratrol reduced vascular senescence cells and the expression of TLR4, MMP3, and MMP9 and prevented alterations of vascular structure in 52-week-old mice. Our findings demonstrated that resveratrol decreased inflammatory protein expression and improved vascular structure in aged mice. Resveratrol inhibited the expression of TLR4 and secretion of MMP3, MMP9, and IL-1. The mechanism of action of resveratrol appears to be associated with the inhibition of TLR4/Syk/NLRP3 activation in ox-LDL-activated platelets.
本研究调查了白藜芦醇对氧化低密度脂蛋白（ox-LDL）激活的血小板中Toll样受体4（TLR4）介导的基质金属蛋白酶3（MMP3）和MMP9表达的影响及其潜在分子机制。本研究使用了人血小板。结果显示，白藜芦醇抑制ox-LDL激活的血小板中TLR4、MMP3和MMP9的表达。TLR4抑制剂CLI-095也抑制ox-LDL和脂多糖（LPS）激活的血小板中MMP3和MMP9的表达及分泌。白藜芦醇与CLI-095联合使用可协同抑制ox-LDL和LPS激活的血小板中MMP3和MMP9的表达。这些发现表明，白藜芦醇诱导的MMP3和MMP9表达抑制与TLR4激活的抑制有关。白藜芦醇还抑制ox-LDL和LPS处理的血小板中脾酪氨酸激酶（Syk）的磷酸化以及核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）的表达和白细胞介素-1（IL-1）的分泌。免疫共沉淀结果显示，白藜芦醇抑制Syk与NLRP3的结合。最后，白藜芦醇减少了52周龄小鼠的血管衰老细胞以及TLR4、MMP3和MMP9的表达，并防止了血管结构的改变。我们的研究结果表明，白藜芦醇可降低衰老小鼠的炎症蛋白表达并改善血管结构。白藜芦醇抑制TLR4的表达以及MMP3、MMP9和IL-1的分泌。白藜芦醇的作用机制似乎与抑制ox-LDL激活的血小板中TLR4/Syk/NLRP3的激活有关。
