Inhibition of ROS and inflammation by an imidazopyridine derivative X22 attenuate high fat diet-induced arterial injuries
Inhibition of ROS and inflammation by an imidazopyridine derivative X22 attenuate high fat diet-induced arterial injuries
复制标题
咪唑并吡啶衍生物 X22 抑制 ROS 和炎症可减轻高脂饮食引起的动脉损伤
DOI：
10.1016/j.vph.2015.05.006
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发表时间：
2015-09-01
影响因子：
4
通讯作者：
Liang, Guang
中科院分区：
文献类型：
--
作者：
Li, Weixin;Wang, Lintao;Liang, Guang
肥胖与动脉的结构和功能改变密切相关。氧化应激和炎症在肥胖引起的心血管疾病的发展中起着关键作用。本课课组先前发现咪唑吡啶衍生物X22对lps刺激的巨噬细胞具有良好的抗炎活性。本研究旨在探讨X22对高脂饮食（HFD）引起的动脉损伤的保护作用及其机制。我们观察到棕榈酸酯（PA）治疗HUVECs诱导活性氧、炎症、细胞凋亡和纤维化显著增加。所有这些变化都被X22以剂量依赖性的方式有效抑制，与nf - κ B失活和Nrf-2活化有关。以10 mg/kg剂量给药X22可显著降低大鼠动脉炎症和氧化应激，最终改善动脉基质重塑和细胞凋亡。10 mg/kg剂量的X22与50 mg/kg剂量的阳性对照姜黄素具有相当的生物活性。X22在体内的有益作用也与其在饲喂hfd的大鼠动脉中增加Nrf2表达和抑制NF-kappa B活化的能力有关。总之，这些结果表明X22可能通过调节nrf2介导的氧化应激和nf - κ b介导的炎症，在治疗肥胖诱导的动脉损伤方面具有治疗潜力。(C) 2015爱思唯尔公司版权所有。
Obesity is strongly associated with the cause of structural and functional changes of the artery. Oxidative stress and inflammation play a critical role in the development of obesity-induced cardiovascular disorders. Our group previously found that an imidazopyridine derivative X22 showed excellent anti-inflammatory activity in LPS-stimulated macrophages. This study was designed to investigate the protective effects of X22 on high fat diet (HFD)-induced arterial injury and its underlying mechanisms. We observed that palmitate (PA) treatment in HUVECs induced a marked increase in reactive oxygen species, inflammation, apoptosis, and fibrosis. All of these changes were effectively suppressed by X22 treatment in a dose-dependent manner, associated with NF-kappa B inactivation and Nrf-2 activation. In HFD-fed rats, administration of X22 at 10 mg/kg significantly decreased the arterial inflammation and oxidative stress, and eventually improved the arterial matrix remodeling and apoptosis. X22 at 10 mg/kg showed a comparable bioactivity with the positive control, curcumin at 50 mg/kg. The in vivo beneficial effects of X22 are also associated with its ability to increase Nrf2 expression and inhibit NF-kappa B activation in the artery of HFD-fed rats. Overall, these results suggest that X22 may have therapeutic potential in the treatment of obesity-induced artery injury via regulation of Nrf2-mediated oxidative stress and NF-kappa B-mediated inflammation. (C) 2015 Elsevier Inc. All rights reserved.