ERK1/2 信号转导通路参与冠心病致心肌炎症的机制

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。

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

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.