急性心肌梗死中Mzb1调节线粒体功能的作用与机制研究

线粒体功能障碍在心肌梗死的发病机制中起着至关重要的作用。深入探究心肌梗死后线粒体功能紊乱的作用机制已成为研究重点。在前期工作中，我们首次发现边缘区B和B1细胞特异性蛋白（Mzb1）定位于心肌细胞线粒体，且在急性心梗时表达显著降低；过表达Mzb1可有效改善受损的心肌细胞；同时，Mzb1可部分恢复受损心肌细胞的线粒体功能；预实验结果发现：在心肌细胞中过表达Mzb1抑制Drp-l的表达，Drp-1是线粒体裂分中的关键蛋白，急性心梗时Drp-1异常升高导致线粒体过度分裂。由此，我们提出科学假说：心肌缺血可能下调Mzb1表达，导致Drp-1表达或功能上调引起粒体动力学及功能紊乱。本项目拟在此基础上，利用延时共聚焦成像、线粒体追踪等技术阐释Mzb1在调节急性心肌梗死后线粒体功能的作用，解析下游及靶点信号通路，揭示Mzb1调控Drp-1介导线粒体功能障碍的新途径，为治疗心肌梗死提供潜在药物靶点。

Mitochondrial dysfunction plays an important role in the pathogenesis of myocardial infarction. In-depth exploration of the mechanism of mitochondrial dysfunction after myocardial infarction has become the focus of research. In our previous work, we found for the first time that marginal zone B and B1 cell specific proteins (Mzb1) were located in the mitochondria of cardiomyocytes and significantly decreased in acute myocardial infarction. Overexpression of Mzb1 could effectively improve the damaged cardiomyocytes. Meanwhile, Mzb1 could partially restore the mitochondrial function of damaged cardiomyocytes. The results of pre-experiment showed that overexpression of Mzb1 inhibited the expression of Drp-l in cardiomyocytes, and Drp-1 was the key protein in mitochondrial cleavage. Abnormal increased of Drp-1 in acute myocardial infarction led to excessive mitochondria fission. Therefore, we propose a scientific hypothesis: myocardial ischemia may induce the downregulation of Mzb1, resulting in the up-regulation or activation of Drp-1, resulting in mitochondrial dynamics imbalance and dysfunction. On this basis, delayed confocal imaging and mitochondrial tracking techniques was performed to explain the mechanism of Mzb1 in regulating mitochondrial function after acute myocardial infarction, to analyze downstream and target signal pathways, and reveal a new way for Mzb1 to regulate Drp-1-mediated mitochondrial dysfunction, and to provide potential drug targets for the treatment of myocardial infarction.