Xiao Jie, Sheng Xi, Zhang Xinyu, Guo Mengqi, Ji Xiaoping
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
Drug Des Devel Ther. 2016 Mar 29;10:1267-77. doi: 10.2147/DDDT.S104925. eCollection 2016.
Curcumin, a polyphenolic compound derived from turmeric, protects against myocardial injury by alleviating oxidative stress, inflammation, apoptosis, and fibrosis. However, the role of curcumin and its mechanism of action on interstitial fibrosis after myocardial infarction (MI) are poorly understood. To clarify, MI was induced by a permanent ligation of the left anterior descending coronary artery in adult mice, and the effects of curcumin were evaluated 4 weeks after the MI event. In vitro, we treated cardiac fibroblasts (CFs) with Ang II, and investigated the anti-fibrotic mechanism of curcumin. Our results showed that curcumin significantly attenuated collagen deposition in vivo and inhibited CF proliferation and migration, and MMP expression. In addition, we found that the down-regulation of SIRT1 after MI was attenuated by curcumin pretreatment, which indicated that the activation of SIRT1 might be involved in the protective action of curcumin. This hypothesis was confirmed by genetic inhibition of SIRT1 (siRNA-SIRT1) in Ang II-treated CFs. Our results provide new insights into the mechanism underlying the anti-fibrotic effects of curcumin in the heart.
姜黄素是一种从姜黄中提取的多酚类化合物,通过减轻氧化应激、炎症、细胞凋亡和纤维化来预防心肌损伤。然而,姜黄素在心肌梗死(MI)后对间质纤维化的作用及其作用机制尚不清楚。为了阐明这一点,通过永久性结扎成年小鼠左冠状动脉前降支诱导MI,并在MI事件发生4周后评估姜黄素的作用。在体外,我们用血管紧张素II处理心脏成纤维细胞(CFs),并研究姜黄素的抗纤维化机制。我们的结果表明,姜黄素在体内显著减轻了胶原沉积,并抑制了CFs的增殖、迁移和MMP表达。此外,我们发现MI后SIRT1的下调被姜黄素预处理减弱,这表明SIRT1的激活可能参与了姜黄素的保护作用。在血管紧张素II处理的CFs中对SIRT1进行基因抑制(siRNA-SIRT1)证实了这一假设。我们的结果为姜黄素在心脏中抗纤维化作用的潜在机制提供了新的见解。