JAK ERK1/2两通路交互作用干预对缺血再灌注心肌p-STAT3和肿瘤坏死因子-α表达的影响

JAK and ERK1/2:how intervention on these two pathways affects myocardial p-STAT3 and TNF-α expression in ischemia-reperfusion

目的研究Janus激酶/信号转导和转录激活子(JAK/STAT)通路和细胞外信号调节激酶1/2(ERK1/2)信号转导通路交互作用对缺血再灌注损伤所致大鼠心肌组织p-STAT3及肿瘤坏死因子(TNF)-α蛋白含量的影响。方法采用Langendorff离体工作心脏灌注模型,大鼠随机分为健康对照组、缺血再灌注组、JAK抑制剂组、ERK1/2抑制剂组、JAK、ERK1/2两通路交互作用组。采用Western印迹法测定心肌p-STAT3蛋白含量,酶联免疫吸附测定法(ELISA)检测试剂盒检测TNF-α蛋白含量。结果与健康对照组相比,心肌组织p-STAT3含量及TNF-α蛋白含量在缺血再灌注组显著升高(P<0.01)。JAK抑制剂组及交互作用组处理后p-STAT3蛋白含量、TNF-α蛋白含量与缺血再灌注组相比明显下降(P<0.01,P<0.05);且2组间比较差异有统计学意义(P<0.05)。而ERK1/2抑制剂组处理后p-STAT3、TNF-α蛋白含量与缺血再灌注组差异无统计学意义(P>0.05)。结论缺血再灌注心肌损伤可使p-STAT3蛋白含量、TNF-α蛋白含量明显升高;抑制JAK/STAT信号转导通路可使其下游蛋白p-STAT3含量及TNF-α蛋白含量明显降低,且同时抑制ERK1/2信号通路对其心肌保护有明显抑制作用。

Objective To investigate how the interaction between Janus kinase / signal transducer and activator of transcription （JAK/STAT） pathway and extracellular signal-regulated kinase 1/2 （ERK1/2） signal transduction pathway affects myocardial p-STAT3 and TNF-α protein contents in isehemia-reperfusion. Methods The Langendorff isolated myocardial ischemia-perfusion model was applied. Forty SD rats were randomly divided into normal control group, ischemia-reperfusion group, JAK inhibitor group, ERK1/2 inhibitor group, and JAK-ERK1/2 interaction group. Myocardial p-STAT3 protein content was determined with Western blotting and myocardial TNF-α protein content with ELISA. Results Compared with normal eontrol group, the myocardial p-STAT3 level and TNF-α protein content in the ischemia-reperfusion group was significantly higher （P〈0.01）. The elevated p-STAT3 level and TNF-α protein content were evidently lowered in JAK inhibitor group and the interaction group compared with the ischemia-reperfusion group （P〈0.01, P〈0.05） and also showed statistical difference when comparison was made between the two groups （P〈0.05）, whereas the p-STAT3 and TNF-α protein in ERK1/2 inhibitor group appeared comparable to the ischemiareperfnsion group （P〉0.05）. Conclusion Myocardial ischemia-reperfusion injury may result in obvious elevation in p- STAT3 and TNF-α protein contents. Inhibition of JAK / STAT signal transduction pathway may significantly reduce p- STAT3 and TNF-α protein content, and at the same time inhibit ERKI/2 signaling pathway in favor of myocardial protection.