ERK5在急性心肌梗死患者中的磷酸化水平及对体外血小板激活的影响

发布时间：2018-04-26 11:17

本文选题：ERK + 血小板　；参考：《复旦学报(医学版)》2017年04期

【摘要】：目的观察急性心肌梗死(acute myocardial infarction,AMI)患者血小板中细胞外信号调节激酶5(extracellular signal-regulated kinase 5,ERK5)的活化水平及其特异性抑制剂XMD8-92对血小板功能的影响,探索ERK5调节血小板活性的分子机制。方法运用Western bolt法检测AMI患者(n=34)和稳定性心绞痛患者(n=33)血小板ERK5、Akt473及Akt308的磷酸化水平;通过检测体外血小板的聚集,测定不同浓度XMD8-92对胶原(collagen)刺激引起的血小板聚集的影响;利用荧光素酶同期检测XMD8-92对血小板致密颗粒分泌的影响;通过检测血小板在纤维蛋白原上的铺展、在血浆中的收缩,评价血小板整合素ɑIIbβ3的活化水平;运用Western bolt法检测聚集反应中XMD8-92对Akt473、Akt308及PTEN370磷酸化的影响。结果 AMI患者组ERK5及Akt473、Akt308磷酸化水平显著升高(P0.05);ERK5抑制剂XMD8-92可抑制胶原诱导的血小板聚集、分泌、栓块收缩及在纤维蛋白原上的铺展等活化指标;XMD8-92处理后血小板Akt473、Akt308及PTEN370磷酸化水平减低。结论 ERK5的激活参与了AMI过程中血小板的活化;ERK5可通过调节PTEN的活性,从而调节Akt的磷酸化水平,进而调控血小板的功能。其特异性抑制剂有望成为新的抗栓药物。
[Abstract]:Objective to investigate the activation level of extracellular signal-regulated kinase (5(extracellular signal-regulated kinase _ 5) ERK5 in platelets of patients with acute myocardial infarction (AMI) and the effect of XMD8-92, a specific inhibitor, on platelet function, and to explore the molecular mechanism of ERK5 regulating platelet activity. Methods the phosphorylation levels of platelets ERK5, Akt473 and Akt308 in patients with AMI and stable angina pectoris were detected by Western bolt method, and the effects of different concentrations of XMD8-92 on platelet aggregation induced by collagen collagenesis were measured. Luciferase was used to detect the effect of XMD8-92 on platelet compact granule secretion, and the activation level of platelet integrin IIb 尾 3 was evaluated by detecting platelet spreading on fibrinogen and contraction in plasma. The effect of XMD8-92 on the phosphorylation of Akt473, Akt308 and PTEN370 in aggregation reaction was detected by Western bolt assay. Results in AMI patients, the phosphorylation levels of ERK5 and Akt473M Akt308 were significantly increased, and the inhibition of platelet aggregation and secretion induced by collagen was inhibited by P0.05AERK5 inhibitor XMD8-92. Activation indexes such as block contraction and fibrinogen spreading reduced the phosphorylation levels of platelet Akt473N Akt308 and PTEN370 after XMD8-92 treatment. Conclusion the activation of ERK5 plays an important role in the process of AMI. ERK5 can regulate the phosphorylation of Akt by regulating the activity of PTEN, and then regulate the function of platelet. Its specific inhibitor is expected to be a new antithrombotic drug.
【作者单位】：复旦大学附属华山医院心内科;
【基金】：国家自然科学基金(81270278) 上海市科委科研计划项目(16411965600)~~
【分类号】：R542.22

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