Dexmedetomidine Protects Cardiomyocytes against Hypoxia/Reoxygenation Injury by Suppressing TLR4-MyD88-NF-κB Signaling.
Dexmedetomidine Protects Cardiomyocytes against Hypoxia/Reoxygenation Injury by Suppressing TLR4-MyD88-NF-κB Signaling.
复制标题
右美托咪定通过抑制 TLR4-MyD88-NF-kappa B 信号传导保护心肌细胞免受缺氧/复氧损伤
DOI：
10.1155/2017/1674613
复制
发表时间：
2017
影响因子：
--
通讯作者：
Ji FH
中科院分区：
文献类型：
--
作者：
Gao JM;Meng XW;Zhang J;Chen WR;Xia F;Peng K;Ji FH
我们先前报道了右美托咪定（DEX）对大鼠缺血/再灌注损伤提供心脏保护。在此，我们评估了Toll样受体4-（TLR 4-）髓样分化初级反应88-（MyD 88-）核因子-κ B（NF-κB）信号转导在DEX介导的心肌细胞缺氧/复氧（H/R）体外模型保护中的作用。 实验在H9 C2细胞和原代新生大鼠心肌细胞中进行。将用载体或DEX预处理的细胞暴露于缺氧1小时，然后再给氧12小时。我们分析了细胞活力和乳酸脱氢酶（LDH）活性，并测定了肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和IL-1β mRNA水平、TLR 4、MyD 88和核NF-κB p65蛋白表达以及NF-κB p65核定位。通过TLR 4 siRNA转染的TLR 4敲低和通过TLR 4 DNA转染的TLR 4过表达用于进一步证实我们的发现。 DEX可保护H/R诱导的细胞损伤和炎症，表现为细胞存活率增加，LDH活性降低，TNF-α、IL-6和IL-1β mRNA水平降低，以及TLR 4和NF-κB蛋白表达降低。TLR 4敲低可部分防止H/R损伤后的细胞损伤，而TLR 4过表达可消除DEX介导的保护作用。 DEX预处理对大鼠心肌细胞H/R损伤的保护作用这种作用部分由TLR 4抑制通过TLR 4-MyD 88-NF-κB信号传导介导。
We previously reported that dexmedetomidine (DEX) offers cardioprotection against ischemia/reperfusion injury in rats. Here, we evaluated the role of toll-like receptors 4- (TLR4-) myeloid differentiation primary response 88- (MyD88-) nuclear factor-kappa B (NF-κB) signaling in DEX-mediated protection of cardiomyocytes using in vitro models of hypoxia/reoxygenation (H/R). The experiments were carried out in H9C2 cells and in primary neonatal rat cardiomyocytes. Cells pretreated with vehicle or DEX were exposed to hypoxia for 1 h followed by reoxygenation for 12 h. We analyzed cell viability and lactate dehydrogenase (LDH) activity and measured tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β mRNA levels, TLR4, MyD88, and nuclear NF-κB p65 protein expression and NF-κB p65 nuclear localization. TLR4 knock-down by TLR4 siRNA transfection and overexpression by TLR4 DNA transfection were used to further confirm our findings. DEX protected against H/R-induced cell damage and inflammation, as evidenced by increased cell survival rates, decreased LDH activity, and decreased TNF-α, IL-6, and IL-1β mRNA levels, as well as TLR4 and NF-κB protein expression. TLR4 knock-down partially prevented cell damage following H/R injury, while overexpression of TLR4 abolished the DEX-mediated protective effects. DEX pretreatment protects rat cardiomyocytes against H/R injury. This effect is partly mediated by TLR4 suppression via TLR4-MyD88-NF-κB signaling.
登录
查看更多内容
右美托咪定减轻原代新生大鼠心肌细胞缺氧/复氧损伤
影响因子：
2.7
作者：
Peng K;Qiu Y;Li J;Zhang ZC;Ji FH
通讯作者：
Ji FH
影响因子：
15.9
作者：
Frantz, S;Kobzik, L;Kelly, RA
通讯作者：
Kelly, RA
影响因子：
37.8
作者：
Oyama, J;Blais, C;Bourcier, T
通讯作者：
Bourcier, T
影响因子：
20.1
作者：
ARCHER, SL;HAMPL, V;WEIR, EK
通讯作者：
WEIR, EK
影响因子：
0.7
作者：
Ren C;Bao YR;Meng XS;Diao YP;Kang TG
通讯作者：
Kang TG