基于PI3K-AKT通路探讨lncRNA在大蒜素减轻心肌再灌注损伤的作用与分子机制

心肌缺血/再灌注（I/R）损伤影响心梗面积，并最终影响远期预后。课题组前期研究证实大蒜素可通过PI3K-AKT通路调节线粒体通透性转换孔（MPTP）开放、降低炎症及氧化应激反应，发挥I/R后心肌保护作用。LncRNA可通过特异性调控作用，广泛参与心血管疾病发生、发展及预后转归，其中lncRNA MALAT1可影响PI3K-AKT通路的功能。目前MALAT1与PI3K-AKT之间的调控作用以及大蒜素具体干预位点、作用方式仍未阐明。据此提出假说：大蒜素可能以MALAT1作为启动因子调控PI3K-AKT/线粒体功能，发挥I/R后心肌保护作用。本课题拟从基因、分子、细胞、组织及器官多层次揭示大蒜素减轻心肌再灌注损伤的分子机制；通过MALAT1/PI3K-AKT/线粒体调节轴阐明大蒜素的疗效机制与具体作用靶点，为大蒜素在急性心梗治疗提供证据，并为中医药治疗心肌I/R损伤提供新的理论依据与治疗方法。

Myocardial ischemic/reperfusion (I/R) injury affects the infarction size, and the long-term prognosis. Our previous study showed that Garlicin could exert the cardial protection after I/R by adjusting mitochondrial permeability transition pore (MPTP) via PI3K-AKT signaling pathway, lowering inflammation and oxidative stress reaction. LncRNA takes part in the occurrence, development and prognosis of vascular diseases by specific regulation effect. LncRNA MALAT1 could affect the function of PI3K-AKT signaling pathway. The adjustment between MALAT1 and PI3K-AKT and the specific intervene sites and mechanisms of Garlicin have not been illustrated. Hence, we propose the hypothesis: Garlicin may exert the myocardial protecting effect after I/R by adjusting PI3K-AKT/MPTP on the basis of lncRNA MALAT1. In this study, we aim to explore the molecular mechanism of Garlicin on ameliorating myocardial reperfusion injury through different perspectives, and illustrate the effective mechanisms and specific intervene sites of Garlicin by MALAT1/PI3K-AKT/MPTP adjusting axis. In that can we provide evidence for the timely use of Garlicin in myocardial infarction and new theory basis and method for traditional Chinese medicine treating I/R.