胞内NOD 1 激活加重心肌梗死及其机制研究
| 作者: |
1刘丹,
1杨慧,
1李汇华
1 首都医科大学病理教研室，北京 100069 |
| 通讯: |
李汇华
Email: hhli1935@yahoo.cn |
| DOI: | 10.3978/j.issn.2095-6959.2013.02.007 |
| 基金: | 国家自然科学基金, HL81025001；81200195 |
摘要
目的:研究细胞内的核苷酸结合的寡聚结构域受体1(nucleotide binding oligomerization domain 1, NOD1) 在小鼠心肌梗死模型中的作用及其机制。目的:对雄性C57/BL6 野生型小鼠15 只永久性结扎冠状动脉前降支复制心肌梗死模型, 随机分为心肌梗死组(MI)、给药组(MI+iE-DAP) 和假手术组(Sham)。MI+iE-DAP 组在造模前30 min 于小鼠腹腔注射NOD1 激动剂γ-D-Glu-mDAP (iEDAP, 100 μg/ 只), MI 组及Sham 组均给予同等剂量的生理盐水。7 d 后取材观察心脏组织的形态学变化及心肌细胞凋亡, 采用免疫组织化学( 免疫组化) 方法检测白细胞介素6(interleukin-6, IL-6)、核因子-κBp65(nuclear transcription factor κBp65, NF-κBp65)、丝裂原激活的蛋白激酶p38(p38 mitogen-activated protein kinase, p38MAPK)、细胞分裂素活化蛋白激酶1/2( Jun N-terminal/stress-activated protein kinases, JNK1/2) 的表达。结果:MI+iE-DAP 组的心肌损伤程度较MI 组严重、炎细胞浸润程度较MI 组多, 炎症因子IL-6 的表达也较MI 组高(P<0.01)。MI+iE-DAP 组心肌凋亡数较MI 组显著增加(P<0.05), MI+iE-DAP 组信号通路NF-κBp65, p38MAPK, JNK1/2 的磷酸化水平均较MI 组增高(P<0.01)。结论:胞内受体NOD1 激动剂iE-DAP 与NOD1 结合后, 可以激活NF-κBp65 信号途径加重心肌梗死过程中的炎症反应, 激活p38MAPK, JNK1/2 加重心肌梗死过程中心肌细胞的损伤。
关键词：
核苷酸结合的寡聚结构域受体1；心肌梗死；炎症；凋亡
Role of intracellular receptor NOD1 activation in execerbating myocardial infarction injury and its underlying mechanism
CorrespondingAuthor: LI Huihua Email: hhli1935@yahoo.cn
DOI: 10.3978/j.issn.2095-6959.2013.02.007
Abstract
Objective: To investigate the role of the activation of nucleotide binding oligomerization domain 1 (NOD1) by γ-D-Glu-mDAP (iE-DAP) in mice model of myocardial infarction (MI) and its underlying mechanisms. Methods: Fifteen male C57/ BL6 mice were randomly divided into the sham group, the MI group, and the MI+iE-DAP group. The mice were injected intraperitoneally with 100 μg iE-DAP (the MI+iE-DAP group) or saline (the sham or MI group) 30 minutes prior to infarction. Histopathology and apoptosis of myocardium, expression of IL-6 and activities of NF-κBp65 and MAPK/p38MAPK /JNK1/2 were measured after 7 days. Results: Pretreatment with iE-DAP in vivo significantly aggravated MI-induced cardiac injury and apoptosis, increased inflammatory cell infiltration, IL-6 expression, and phosphorylation of P65, P38, and JNK compared with the MI group (P<0.01). Conclusion: The activation of NOD1 by iE-DAP exacerbates the inflammation and damage of myocardium associates with NF-κBp65, p38MAPK, and JNK1/2 signaling pathway.