Blocking the MyD88-dependent pathway protects the myocardium from ischemia/reperfusion injury in rat hearts
Blocking the MyD88-dependent pathway protects the myocardium from ischemia/reperfusion injury in rat hearts
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DOI：
10.1016/j.bbrc.2005.10.068
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发表时间：
2005-12-16
影响因子：
3.1
通讯作者：
Li, CF
中科院分区：
文献类型：
--
作者：
Hua, F;Ha, TZ;Li, CF
我们通过在心脏缺血（45 分钟）和再灌注（4 小时）前 3 天将 Ad5-dnMyD88 转染到大鼠（n = 8）的心肌中，检查阻断 MyD88 介导的途径是否可以保护心肌免受缺血/再灌注（I/R）损伤。 Ad5-GFP 作为对照 (n = 8)。一组大鼠（n = 8）在未转染的情况下接受 I/R。与 I/R 组相比，Ad5-dnMyD88 的转染使梗塞面积显着减少 53.6%（15.1 +/- 3.02 vs 32.5 +/- 2.59），而 Ad5-GFP 的转染不影响 I/R 诱导的心肌损伤（35.4 +/- 2.59 vs 32.5 +/- 2.59）。 Ad5-dnMyM 的转染可显着抑制 I/R 增强的 NF kappa B 活性 50%，并使磷酸-Akt 水平分别增加 35.6% 和 BCL-2 水平 81%。 Ad5-dnMyD88 组 I/R 后心肌细胞凋亡显着减少 59%。结果表明，NF kappa B 激活途径的抑制和 Akt 信号途径的激活可能是显性失活 MyD88 转染的保护作用的原因。 (c) 2005 Elsevier Inc. 保留所有权利。
We examined whether blocking the MyD88 mediated pathway could protect myocardium from ischemia/reperfusion (I/R) injury by transfecting Ad5-dnMyD88 into the myocardium of rats (n = 8) 3 days before the hearts were subjected to ischemia (45 min) and reperfusion (4 h). Ad5-GFP served as control (n = 8). One group of rats was (n = 8) subjected to I/R without transfection. Transfection of Ad5-dnMyD88 significantly reduced infarct size by 53.6% compared with the I/R group (15.1 +/- 3.02 vs 32.5 +/- 2.59) while transfection of Ad5-GFP did not affect I/R induced myocardial injury (35.4 +/- 2.59 vs 32.5 +/- 2.59). Transfection of Ad5-dnMyM significantly inhibited I/R-enhanced NF kappa B activity by 50% and increased the levels of phospho-Akt by 35.6% and BCL-2 by 81%, respectively. Cardiac myocyte apoptosis after I/R was significantly reduced by 59% in the Ad5-dnMyD88 group. The results demonstrate that both inhibition of the NF kappa B activation pathway and activation of the Akt signaling pathway may be responsible for the protective effect of transfection of dominant negative MyD88. (c) 2005 Elsevier Inc. All rights reserved.