Xie Liang, He Songqing, Kong Na, Zhu Ying, Tang Yi, Li Jianhua, Liu Zhengbing, Liu Jing, Gong Jianbin
Cell Physiol Biochem. 2018;47(4):1389-1398. doi: 10.1159/000490828. Epub 2018 Jun 19.
BACKGROUND/AIMS: Toll-like receptors (TLRs) have been implicated in myocardial ischemia/ reperfusion (I/R) injury. We examined the effect of CpG-oligodeoxynucleotide (ODN) on myocardial I/R injury.
Male Sprague-Dawley rats were treated with either CpG-ODN or control ODN 1 h prior to myocardial ischemia (30 min) followed by reperfusion. Rats treated with phosphate-buffered saline (PBS) served as I/R controls (n = 8/group). Infarct size was determined by 2,3,5-triphenyltetrazolium chloride and Evans blue straining. Cardiac function was examined by echocardiography before and up to 14 days after myocardial I/R.
CpG-ODN administration significantly increased infarct size and reduced cardiac function and survival rate after myocardial I/R, compared to the PBS-treated I/R group. Control-ODN did not alter I/R-induced myocardial infarct size, cardiac dysfunction, and survival rate. Additionally, CpG-ODN promoted I/R-induced myocardial apoptosis and cleaved caspase-3 levels in the myocardium. CpG-ODN increased TLR9 activation and p38 phosphorylation in the myocardium. In vitro data also suggested that CpG-ODN treatment induced TLR9 activation and p38 phosphorylation. Importantly, p38 mitogen-activated protein kinase (MAPK) inhibition abolished CpG-ODN-induced cardiac injury.
CpG-ODN, the TLR9 ligand, accelerates myocardial I/R injury. The mechanisms involve activation of the TLR9-p38 MAPK signaling pathway.
背景/目的：Toll样受体（TLRs）与心肌缺血/再灌注（I/R）损伤有关。我们研究了CpG-寡脱氧核苷酸（ODN）对心肌I/R损伤的影响。
雄性Sprague-Dawley大鼠在心肌缺血（30分钟）前1小时接受CpG-ODN或对照ODN治疗，随后进行再灌注。用磷酸盐缓冲盐水（PBS）处理的大鼠作为I/R对照（每组n = 8）。通过2,3,5-三苯基氯化四氮唑和伊文思蓝染色确定梗死面积。在心肌I/R前及之后长达14天通过超声心动图检查心脏功能。
与PBS处理的I/R组相比，给予CpG-ODN显著增加了心肌I/R后的梗死面积，降低了心脏功能和生存率。对照ODN未改变I/R诱导的心肌梗死面积、心脏功能障碍和生存率。此外，CpG-ODN促进了I/R诱导的心肌细胞凋亡并增加了心肌中裂解的半胱天冬酶-3水平。CpG-ODN增加了心肌中TLR9的激活和p38磷酸化。体外数据也表明CpG-ODN处理诱导了TLR9激活和p38磷酸化。重要的是，p38丝裂原活化蛋白激酶（MAPK）抑制消除了CpG-ODN诱导的心脏损伤。
TLR9配体CpG-ODN加速心肌I/R损伤。其机制涉及TLR9-p38 MAPK信号通路的激活。
