Basic and clinical studies have demonstrated that the free radical scavenger edaravone has cytoprotective effects on acute myocardial infarction (AMI) but the underlying mechanism is not fully understood. The aim of this research is to explore the effect of edaravone on the apoptotic process involving the JAK2/STAT3 signaling pathway. AMI in rats was established by left anterior descending coronary artery ligation. Two hours after AMI model established rats were treated with edaravone, edaravone plus AG490, physiological saline, respectively. We detected antioxidant effects by reduced glutathione (GSH), glutathione S-transferase (GST), and Glutathione Peroxidase (GSHPx) Activity. The expressions of t-JAK2, p-JAK2, t-STAT3, p-STAT3 and cleaved caspase-3 were examined by western blot. The mRNA levels for Bcl-2, Bax, Fas, and FasL were measured by RT-PCR and apoptosis was assessed by TUNEL. Edaravone significantly improved hemodynamics after AMI (p < 0.05) and reduced the total infarct volumes (p < 0.05). Compared with Sham rats, the mRNA of Bax, Fas, and FasL increased in different degrees in the AMI group, however, the mRNA of Bcl-2 and the ratio of Bcl-2/Bax decreased, especially the myocardial apoptosis index significantly increased in AMI hearts (all p < 0.05). After treatment with edaravone, the mRNA levels of Bcl-2 and the ratio of Bcl-2/Bax significantly upregulated whereas Bax, Fas, FasL apparently decreased, and the protein expressions of p-JAK2 and p-STAT3 dramatically increased (p < 0.05). In addition, cotreatment with JAK2 inhibitor AG490 abolished the effects of edaravone. We conclude that edaravone attenuated myocardial apoptosis induced by AMI via JAK2/STAT3 signaling pathway.

基础和临床研究表明，自由基清除剂依达拉奉对急性心肌梗塞（AMI）具有细胞保护作用，但其潜在机制尚未完全了解。这项研究的目的是探讨依达拉奉对涉及JAK2 / STAT3信号通路的凋亡过程的影响。大鼠左前降支结扎可建立大鼠AMI。建立AMI模型后两小时，分别用依达拉奉，依达拉奉加AG490，生理盐水处理大鼠。我们通过降低谷胱甘肽（GSH），谷胱甘肽S-转移酶（GST）和谷胱甘肽过氧化物酶（GSHPx）活性来检测抗氧化作用。通过western blot检测t-JAK2，p-JAK2，t-STAT3，p-STAT3和裂解的caspase-3的表达。Bcl-2，Bax，Fas，RT-PCR检测FasL和FasL，TUNEL检测凋亡。依达拉奉显着改善AMI后的血液动力学（p  <0.05）并减少了总梗死体积（p  <0.05）。与Sham大鼠相比，AMI组Bax，Fas和FasL的mRNA均有不同程度的升高，而Bcl-2的mRNA和Bcl-2 / Bax的比值降低，特别是心肌细胞凋亡指数明显升高。 AMI心（均p  <0.05）。依达拉奉治疗后，Bcl-2的mRNA水平和Bcl-2 / Bax的比值显着上调，而Bax，Fas，FasL明显降低，p-JAK2和p-STAT3的蛋白表达显着增加（p  <0.05 ）。另外，与JAK2抑制剂AG490共同处理消除了依达拉奉的作用。我们得出的结论是，依达拉奉通过以下途径减轻了AMI诱导的心肌细胞凋亡： JAK2 / STAT3信号通路。