Hydroxysafflor yellow A alleviates myocardial ischemia/reperfusion in hyperlipidemic animals through the suppression of TLR4 signaling.
Hydroxysafflor yellow A alleviates myocardial ischemia/reperfusion in hyperlipidemic animals through the suppression of TLR4 signaling.
复制标题
DOI：
10.1038/srep35319
复制
发表时间：
2016-10-12
影响因子：
4.6
通讯作者：
Fang W
中科院分区：
文献类型：
--
作者：
Han D;Wei J;Zhang R;Ma W;Shen C;Feng Y;Xia N;Xu D;Cai D;Li Y;Fang W
高脂血症通过刺激过度的炎症反应加重心肌缺血/再灌注（MI/R）损伤。因此，阻断炎症信号是治疗MI/R合并高脂血症的一种潜在方法。本文从红花中提取单体羟基红花黄A (hydroxyysafflor yellow A， HSYA)，研究其对炎症信号的调节对MI/R合并高脂血症损伤的缓解作用。高脂饮食引起的高脂血症加重了MI/R介导的心脏损伤（梗死面积、CK-MB和LDH活性升高），激活了心脏中TLR4的过度表达，过度释放炎症因子（LPS、TNF-α和IL-1β）。HSYA可抑制TLR4的过表达，减轻MI/R合并高脂血症引起的心脏损害。此外，HSYA对TLR4基因敲除小鼠MI/R损伤的影响较小，说明HSYA通过抑制TLR4保护MI/R。体外缺氧/再氧化（H/R）与LPS共存模型对新生大鼠心室肌细胞（nrvm）的损伤较H/R损伤严重。HSYA可降低H/R + LPS损伤nrvm中炎性细胞因子的过度分泌，下调TLR4和NF-κB的过度表达。综上所述，HSYA通过抑制TLR4减轻心肌炎症损伤，为高脂血症相关MI/R提供了一种替代药物。
Hyperlipidemia aggravates myocardial ischemia/reperfusion (MI/R) injury through stimulating excessive inflammatory response. Therefore, blockade of inflammatory signal is a potential therapeutic management for MI/R complicated with hyperlipidemia. Hydroxysafflor yellow A (HSYA, a monomer extracted from Carthamus tinctorius L.), was studied in this article to address that the regulation of inflammatory signal would alleviate MI/R combined with hyperlipidemia injury. High-fat diet induced hyperlipidemia worsened MI/R mediated heart injury (elevation of infarct size, CK-MB and LDH activity), activated TLR4 over-expression in hearts, released inflammatory cytokines (LPS, TNF-α and IL-1β) excessively. HSYA administration suppressed the over-expression of TLR4 and alleviated heart damage caused by MI/R complicated with hyperlipidemia. Furthermore, HSYA had little influence on MI/R injury in TLR4-knockout mice, which indicated that HSYA protected MI/R through TLR4 inhibition. In vitro, hypoxia/reoxygenation (H/R) coexisting with LPS model in neonatal rat ventricular myocytes (NRVMs) induced serious damage compared with H/R injury to NRVMs. HSYA decreased excessive secretion of inflammatory cytokines, down-regulated over-expression of TLR4 and NF-κB in H/R + LPS injured NRVMs. In conclusion, HSYA alleviated myocardial inflammatory injury through suppressing TLR4, offering an alternative medication for MI/R associated with hyperlipidemia.
登录
查看更多内容
影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
5.9
作者：
Matsumoto S;Gotoh N;Hishinuma S;Abe Y;Shimizu Y;Katano Y;Ishihata A
通讯作者：
Ishihata A
影响因子：
6.5
作者：
Clemente-Postigo, M.;Queipo-Ortuno, M. I.;Tinahones, F. J.
通讯作者：
Tinahones, F. J.
影响因子：
20.1
作者：
Kapadia, SR;Oral, H;Mann, DL
通讯作者：
Mann, DL
影响因子：
4.4
作者：
Sabroe, I;Jones, EC;Dower, SK
通讯作者：
Dower, SK