模式识别受体NOD2在小鼠心肌梗死后心肌纤维化中的作用及机制  

The Role of Intracellular Receptor NOD2 in Myocardial Fibrosis after Myocardial Infarction and Its Underlying Mechanism

作　　者：刘瑜[1] 杨慧[1] 田翠[2] 李汇华[2] 梁海峰[3] 王红霞[2] Liu yu Yang hui Tian cui Li hui-hua Liang hai-feng Wang hong-xia(Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China Cardiological Center, Fuxing Hospital Affiliated to Capital Medical University, Beijing 100038, China.)

机构地区：[1]首都医科大学基础医学院病理学系,北京市100069 [2]首都医科大学基础医学院生理学与病理生理学系,北京市100069 [3]首都医科大学附属复兴医院心脏中心,北京市100038

出　　处：《中国分子心脏病学杂志》2016年第5期1854-1856,共3页Molecular Cardiology of China

基　　金：国家自然科学青年基金项目(81500320);首都医科大学基础-临床科研合作基金(14JL69;15JL88;16JL39);2014年度首都医科大学科研基金项目(自然类)(2014ZR10)

摘　　要：目的探讨模式识别受体(nucleotide binding oligomerization domain 2,NOD2)在小鼠心肌梗死后心肌纤维化中的作用及其分子机制。方法雄性C57/BL6野生型小鼠18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(myocardial infarction,MI)组、NOD2激动剂胞壁酰二肽(muramyl dipeptide,MDP)组(MI+MDP)及假手术组(Sham),其中MI+MDP组在造模前30min给予小鼠腹腔注射MDP(100μg/只),MI组及Sham组均给予同等剂量的生理盐水。一周后取材,Masson染色观察心脏纤维化的程度,HE染色观察心肌组织形态学改变,免疫组化染色观察巨噬细胞的浸润情况,RT-PCR方法检测白细胞介素-6(interleukin-6,IL-6)和单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)表达,Western blot方法检测核因子-κB(nuclear transcription factor-κB,NF-κB)的蛋白表达水平。结果与心肌梗死组比较,NOD2激动剂组巨噬细胞浸润增多,IL-6和MCP-1表达水平增加,NF-κB/p65的表达增加,心肌间质纤维化程度加重。结论NOD2可能通过激活NF-κB/p65信号通路,介导炎症反应参与心肌梗死后心肌纤维化过程。Objective To investigate the role of the activation of nucleotide binding oligomerization domain 2 （NOD2） by muramyl dipeptide （MDP） in mice model of myocardial infarction （MI） and its underlying mechanisms. Methods Eighteen male C57/BL6 mice were randomly divided into the sham group, the MI group, and the MI＋MDP group. The mice were injected intraperitoneally with 100μg MDP （the MI＋MDP group） or saline （the sham or MI group） 30 minutes prior to infarction. Cardiac fibrosis in the mice was detected with Masson staining. Morphological change of the myocardium was observed with HE staining. Macrophage infiltration was measured with immunohistochemical staining. Expressions of myocardial interleukin 6 （IL-6） and monocyte chemotactic protein 1 （MCP-1） mRNA were detected by RT-PCR, Protein level of nuclear transcription factor-roB （NF-κB） was measured by Western blot analysis after 7 days. Results Pretreatment with MDP in vivo significantly aggravated MI-induced cardiac fibrosis, increased inflammatory cell infiltration, IL-6 and MCP- 1 expression, and phosphorylation of NF-lcB, compared with the MI group （P〈0.05）. Conclusion NOD2 participates cardiac fibrosis after cardiac infarction in mice by mediating inflammatory reactions through NF-κB signaling pathway.

关 键 词：核苷酸结合寡聚化结构域2 心肌梗死 炎症 纤维化 

分 类 号：R542.22[医药卫生—心血管疾病]