成纤维细胞生长因子21通路激活与心脏术后心肌保护结果的研究

Oxidative stress mediated by reactive oxygen species plays a striking role in the pathogenesis of ischemiareperfusion injury. Activation of fibroblast growth factor 21 pathway can reduce oxidative stress level when the body underwent ischemia reperfusion challenge. This activation confers cardioprotection effect. 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, in vitro 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.

氧化应激是导致心肌缺血再灌注损伤的主要原因。成纤维细胞生长因子21（FGF21）通路激活能降低机体氧化应激反应水平，在经历缺血再灌注损伤时使活性氧类物质产生减少，产生心肌保护效果。最新研究发现果糖摄入能快速激活机体FGF21通路，使循环FGF21水平在短时间内迅速上升，且FGF21增加水平较其它刺激更显著。但是，既往研究未报道果糖摄入与心肌保护效果的关系。因此，我们推测果糖摄入能快速激活机体FGF21通路产生心肌保护效果。为证实这一假设，我们用果糖激活FGF21通路，使用大鼠缺血再灌注模型和临床病例，采用分子生物学、酶联免疫学、免疫印迹，实时定量PCR等技术，收集临床标本和病例资料，从心肌组织、整体动物及临床三个层次，观察果糖激活FGF21通路对心肌保护效果的影响及其信号传导通路。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。

氧化应激是导致心肌缺血再灌注损伤的主要原因。成纤维细胞生长因子21（FGF21）通路激活能降低机体氧化应激反应水平，在经历缺血再灌注损伤时使活性氧类物质产生减少，产生心肌保护效果。本研究使用果糖摄入激活机体FGF21通路，检测发现循环血中FGF21 含量上升；心肌组织应激通路相关指标β-Klotho，PI3K较对照组下降，应激指标SOD2表达显著降低。但未在整体动物水平发现产生显著的心肌保护效果。本课题从一个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新的心肌保护策略的研发提供依据。