酪氨酰转运RNA合成酶激活对心肌保护效果影响的研究

Stress can reduce myocardial ischemia/reperfusion injury through the mechanism of preconditioning，and show myocardial protection effect. Tyrosyl transfer-RNA synthetase (TyrRS) plays a key role in the nucleus. The latest study found that specific activation of TyrRS enables it to play a new role in the nucleus. TyrRS activation in turn activates poly ADP-ribose polymerase 1(PARP1) which causes downstream activation of key stress signaling pathways. The generated stress is stronger than that induced by traditional stimulations. So far there is no report on whether TyrRS activation can produce myocardial protection effect. Therefore, we hypothesized that specific activation of TyrRS will produce myocardial protection effect. To verify this hypothesis, we will specifically activate TyrRS to study its effect on myocardial protection by using myocardial cells, cardiac tissues, whole animal models and clinical data. Molecular biology techniques, ELISA, immunoblotting, and clinical data will be used to study the related mechanism and signal transduction pathway. This research will study myocardial protection from a whole new signaling pathway, and its results will provide new evidences for the reduction of myocardial ischemia reperfusion injury and the development of new myocardial protection strategies during cardiac surgery.

应激能通过预适应机制减轻心肌缺血再灌注损伤，表现出心肌保护效果。酪氨酰转运RNA合成酶（TyrRS）主要在细胞核里发挥作用，最新研究发现特异性激活TyrRS使其在细胞核内发挥新的作用，能激活产生应激的关键通路（聚腺苷二磷酸核糖聚合酶1（PARP-1）通路），且产生的应激效果较传统的刺激强。但是，迄今国内外尚无报道TyrRS激活是否会产生心肌保护效果。因此，我们推测特异性激活TyrRS会产生心肌保护效果。为证实这一假设，我们将TyrRS特异性激活，使用大鼠缺血模型和临床病例，采用分子生物学、酶联免疫学、免疫印迹等技术，收集临床资料，从心肌细胞－离体心脏组织－整体动物及临床四个层次，观察TyrRS特异性激活对心肌保护的影响，研究相关机制及信号传导通路。本课题将从全新的通路对心肌保护进行研究，为减少心肌缺血再灌注损伤及心脏外科新的心肌保护策略的研发提供依据。

应激能通过预适应机制减轻心肌缺血再灌注损伤，表现出心肌保护效果。酪氨酰转运RNA合成酶（TyrRS）主要在细胞核里发挥作用，研究发现特异性激活TyrRS能激活产生应激的关键通路，且产生的应激效果较传统的刺激强。但尚无报道TyrRS激活是否会产生心肌保护效果。本研究发现在心肌细胞及组织中激活TyrRS后应激指标水平上升，经历缺氧后心肌损伤相关指标上升较低。但临床研究未发现激活TyrRS会产生心肌保护效果，予以调整研究方向。冠状动脉旁路移植术术后血糖变化与成纤维细胞生长因子21显著相关。FGF21是重要的糖代谢调控因子，因此可作为预测术后血糖变化的潜在标志物。冠状动脉造影后48小时以内进行心脏瓣膜手术的患者发生急性肾功能损伤的比例较48小时以后手术的患者显著升高。为减少急性肾损伤的发生率，获得更好的临床结果，建议择期瓣膜手术在冠状动脉造影48小时后进行。携带ALDH2*2突变基因型的患者术后心肌保护效果更差。这为预测冠状动脉旁路移植术患者预后以及制定个性化的心肌保护方案提供了依据。