Deng Zu Yue, Hu Meng Mei, Xin Yan Fei, Gang Chen
Zhejiang University of Technology, Hangzhou, 310004, Zhejiang, China,
Inflamm Res. 2015 May;64(5):321-32. doi: 10.1007/s00011-015-0810-4. Epub 2015 Apr 2.
Atherosclerosis (AS) is an inflammatory disease involved in vascular inflammatory injury. The inflammasome is an important part of inflammatory diseases and participates in the vascular inflammatory injury. Resveratrol (RSV) possesses anti-inflammatory activities, but its effects on inflammasomes during vascular injury remain unclear. This study focused on the effects and mechanisms of RSV on inflammasomes during vascular injury.
Male Sprague-Dawley rats were treated with a purified diet or cholesterol-enriched diet combined with vitamin D2 (VD; 1.8 million units/kg/days, Po) and saline or RSV (50 mg/kg/days, Po) daily for 5 weeks. The concentrations and enzyme activities of related indicators were measured by a spectrophotometer or ELISA kit. Their gene and protein expression levels were analyzed by reverse transcription-polymerase chain reaction and Western blot, respectively.
Upon administration with RSV, rats with combined hyper cholesterol and VD demonstrated the following changes: the vascular histopathological changes were relieved, and the level of the von Willebrand factor decreased. The level of serum IL-1β, a marker of inflammasome activation, significantly decreased. The mRNA and protein expression levels of the three components of inflammasomes, namely, NOD-like receptor pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, and caspase-1, were downregulated. The effects of RSV were closely related to hypolipidemia (decrease in the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol combined with the expression of the lectin-like ox-LDL receptor and increase in high-density lipoprotein cholesterol), antioxidation (decrease in MDA levels and increase in SOD and GPx activities), and anti-inflammation (downregulation of the expression of IL-1β, intracellular adhesion molecule-1, and monocyte chemotactic protein-1). The mechanisms for the downregulation of NF-κB p65 and p38 MAPK expression, as well as the upregulation of SIRT1 expression, were analyzed.
This study proved that RSV inhibited inflammasome activation to protect vascular injury in vivo. RSV exhibited therapeutic potential in the treatment of vascular injury.
动脉粥样硬化（AS）是一种涉及血管炎症损伤的炎症性疾病。炎性小体是炎症性疾病的重要组成部分，参与血管炎症损伤。白藜芦醇（RSV）具有抗炎活性，但其在血管损伤过程中对炎性小体的影响尚不清楚。本研究聚焦于RSV在血管损伤过程中对炎性小体的影响及其机制。
将雄性Sprague-Dawley大鼠分为两组，一组给予纯化饮食，另一组给予富含胆固醇的饮食并联合维生素D2（VD；180万单位/千克/天，经口灌胃），同时每天分别给予生理盐水或RSV（50毫克/千克/天，经口灌胃），持续5周。通过分光光度计或ELISA试剂盒测定相关指标的浓度和酶活性。分别采用逆转录-聚合酶链反应和蛋白质免疫印迹法分析其基因和蛋白表达水平。
给予RSV后，合并高胆固醇和VD的大鼠出现以下变化：血管组织病理学改变减轻，血管性血友病因子水平降低。炎性小体激活标志物血清IL-1β水平显著降低。炎性小体的三个组成部分，即含NOD样受体吡咯结构域蛋白3、含半胱天冬酶招募结构域的凋亡相关斑点样蛋白和半胱天冬酶-1的mRNA和蛋白表达水平均下调。RSV的作用与降血脂（总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平降低，凝集素样氧化型低密度脂蛋白受体表达增加，高密度脂蛋白胆固醇增加）、抗氧化（丙二醛水平降低，超氧化物歧化酶和谷胱甘肽过氧化物酶活性增加）和抗炎（IL-1β、细胞间黏附分子-1和单核细胞趋化蛋白-1表达下调）密切相关。分析了NF-κB p65和p38 MAPK表达下调以及SIRT1表达上调的机制。
本研究证明RSV在体内可抑制炎性小体激活以保护血管损伤。RSV在治疗血管损伤方面具有治疗潜力。
