天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (8): 938-942.doi: 10.11958/20150269

• 专题研究-心血管 • 上一篇    下一篇

ERK1/2 信号转导通路参与冠心病致心肌炎症的机制

王菁1 ， 徐美林1 ， 畅昶2 ， 丛洪良1△   

  1. 1天津市胸科医院 （邮编300222）； 2河南科技大学第一附属医院
  • 收稿日期:2015-10-29 修回日期:2016-02-16 出版日期:2016-08-15 发布日期:2016-08-22
  • 通讯作者: 丛洪良E-mail:hongliangcong@126.com E-mail:janewjing@163.com
  • 作者简介:王菁 （1975）， 女， 副主任医师， 硕士， 主要从事心血管系统病理研究
  • 基金资助:
    天津市卫生局科技基金 （2011KZ59）

Mechanisms of ERK1/2 signaling pathway participate in inflammatory reaction caused by coronary heart disease

WANG Jing1 , XU Meilin1 , CHANG Chang2 , CONG Hongliang1△   

  1. 1 Tianjin Chest Hospital, Tianjin 300222, China； 2 the First Affiliated Hospital of Henan University of Science and Technology
  • Received:2015-10-29 Revised:2016-02-16 Published:2016-08-15 Online:2016-08-22
  • Contact: △Corresponding Author E-mail: hongliangcong@126.com E-mail:janewjing@163.com

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摘要： 摘要： 目的 探讨细胞外信号调节激酶 （ERK） 1/2 信号转导通路参与冠状动脉粥样硬化性心脏病 （冠心病） 致心肌炎症的机制。方法 45 例尸检病例分为 3 组： 冠心病死亡组、 冠心病组、 对照组 （每组 15 例）。 HE 染色和免疫组织化学染色白细胞共同抗原 （CD45） 并观察心肌组织炎症细胞浸润情况； 免疫组织化学染色和 Western blot 检测心肌组织的总 ERK 1/2 （t-ERK1/2） 和磷酸化 ERK 1/2 （p-ERK1/2） 的蛋白表达及分布； 荧光定量 RT-PCR 分析肿瘤坏死因子 （TNF） -α表达水平； 应用电泳迁移率转变分析 （EMSA） 评价核因子 （NF） -κB 的活性。结果 与冠心病组、 对照组比较， 冠心病死亡组心肌炎症细胞数、 心肌组织 p-ERK1/2 蛋白表达、 TNF-α mRNA 表达及 NF-κB 活性明显增高 （均 P＜0.05）。Western blot 检测冠心病死亡组 p-ERK1/2 和 TNF-α mRNA、 心肌炎细胞计数均呈正相关 （r 分别为 0.675、 0.893， 均 P＜0.01）。结论 ERK1/2 信号转导通路激活是冠心病致心肌炎症反应的重要机制， 抑制 ERK1/2 信号转导通路可能成为冠心病防治的潜在新靶点。

关键词: 丝裂原活化蛋白激酶 1, 冠状动脉疾病, 心肌, 炎症, 肿瘤坏死因子α, NF-κB, 细胞外信号调节激酶 1/2

Abstract: Abstract： Objective To investigate the effects of ERK1/2 signaling pathway on coronary atherosclerosis-associated inflammatory reaction in autopsy cases. Methods Forty-five autopsy cases were divided into three groups: coronary artery disease (CHD)- associated death group, CHD group and control group (n=15 for each group). The inflammatory cell infiltration in myocardial tissues was observed through staining leucocyte common antigen (CD45) by HE and immunohistochemistry method. The protein expression level and distribution in extracellular signal-regulated kinase1/2 (t- ERK1/2) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) of myocardial tissues were detected by immunohistochemistry and Western-blot assay. The expression level of tumor necrosis factor α (TNF-α) was determined using semiquantitative RT-PCR analysis. The activity of nuclear factor (NF)-κB was assessed using electrophoretic mobility shift assay (EMSA). Results Compared with CHD and control groups, myocardial inflammatory cell counts, phosphorylation of ERK1/2, TNF- α mRNA expression and NF- κB activation were significantly increased in CHD- associated death group (P < 0.05). Western blot analysis showed that the phosphorylation of ERK1/2 was positively correlated with expression of TNF-α mRNA and the number of inflammatory cells in CHD-associated death group (r=0.675, P < 0.01; r=0.893, P < 0.01). Conclusion Results reveal that the activation of ERK1/2 signaling pathway is considered as an important mechanism for coronary atherosclerosis caused myocardial inflammatory reaction, which indicates that the inhibition of ERK1/2 signal transduction pathway may become a potential new target for prevention and treatment of atherosclerotic coronary infarction.

Key words: mitogen-activated protein kinase 1, coronary artery disease, myocardium, inflammation, tumor necrosis factor-alpha, NF-kappa B, extracellular signal-regulated kinases 1/2