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二氨基庚二酸激活NOD1信号通路对心肌缺血再灌注损伤的影响
作者:柳磊1  张武2  李召彬1  李滨1  徐贯杰3  王园园1  王金星4 
单位:1. 河北医科大学第三医院 心脏外科, 河北 石家庄 050051;
2. 安岳县人民医院 心血管内科, 四川 资阳 642350;
3. 河北医科大学第三医院 麻醉科, 河北 石家庄 050051;
4. 河北医科大学第三医院 实验中心, 河北 石家庄 050051
关键词:心肌缺血再灌注损伤 核苷酸结合寡聚化结构域蛋白1 二氨基庚二酸 NF-κB信号通路 小鼠 
分类号:R542.2;R-33
出版年·卷·期(页码):2018·37·第四期(691-696)
摘要:

目的:探讨二氨基庚二酸(DAP)激活核苷酸结合寡聚化结构域蛋白1(NOD1)信号通路对心肌缺血再灌注(I/R)损伤的影响。方法:将40只C57/BL6雄性小鼠随机分为4组,即假手术组、I/R组、DAP组和I/R+DAP组,每组10只。对I/R组和I/R+DAP组小鼠进行心肌缺血再灌注模型制备,假手术组进行相同的手术操作,但只穿线不结扎,DAP组和I/R+DAP组小鼠在冠状动脉结扎前30 min腹腔注射DAP,假手术组和I/R组小鼠注射等剂量的生理盐水;观察各组小鼠心肌梗死、心肌细胞凋亡、炎症反应及NF-κB p65磷酸化情况。结果:I/R组NOD1 mRNA和NOD1蛋白表达水平均显著高于假手术组(P<0.05);I/R组梗死面积比值明显高于假手术组,且I/R+DAP组小鼠梗死面积最高(P<0.05),而DAP组与假手术组差异无统计学意义;I/R组和I/R+DAP组TUNEL阳性细胞数显着高于假手术组,I/R+DAP组阳性细胞数最多(P<0.05),而DAP组与假手术组差异无统计学意义;I/R组和I/R+DAP组炎症细胞浸润数明显多于假手术组,I/R+DAP组小鼠最高(P<0.05);I/R组和I/R+DAP组磷酸化的NF-κB p65蛋白水平显著高于假手术组,且I/R+DAP组最高(P<0.05)。结论:DAP激活NOD1可加重缺血再灌注损伤后小鼠心脏心肌细胞的梗死面积,增加心肌细胞的凋亡和炎症反应,该机制与NF-κB信号通路的激活有关。

Objective:To investigate the effect of diaminopimelate (DAP) activated NOD1 signaling pathway on myocardial ischemia/reperfusion (I/R) injury. Methods:40 C57/BL6 male mice were randomly divided into four groups (n=10):sham group, I/R group, DAP group and I/R+DAP group. Mice in I/R group and I/R+DAP group were treated with myocardial ischemia-reperfusion model, sham group was treated with the same operation, but only threaded without deligation. DAP group and I/R+DAP group were treated with intraperitoneal injection of DAP at 30 min before coronary artery ligation, sham operation group and I/R group, mice in sham group and I/R group were injected with normal saline. Myocardial infarction, myocardial apoptosis, inflammatory reaction and NF-κB p65 phosphorylation were observed in each group. Results:The expression of NOD1 mRNA and NOD1 protein in I/R group were significantly higher than those in sham operation group (P<0.05). The infarct size in I/R group was significantly higher than that in sham operation group, and the infarct size of I/R+DAP group was the highest (P<0.05). The number of TUNEL positive cells in I/R group and I/R+DAP group were significantly higher than that in sham group, and the number of positive cells in I/R+DAP group was the highest (P<0.05).The infiltration rate of inflammatory cells in I/R group and I/R+DAP group was significantly higher than that in sham group, and I/R+DAP group were the highest (P<0.05). The levels of phosphorylated NF-κB p65 protein in I/R group and I/R+DAP group were significantly higher than those in the sham operation group, and I/R+DAP group were the highest (P<0.05). Conclusion:This study demonstrates that activation of NOD1 through DAP can aggravate the infarct size of cardiac cardiomyocytes and increase the apoptosis and inflammatory response of cardiomyocytes in mice after ischemia/reperfusion injury, and which is related to the activation of NF-κB signaling pathway.

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