基于FUNDC1 介导的线粒体自噬探讨Rg1-R1 组分药对对心肌微循环缺血再灌注损伤机制研究

心肌微循环破坏是心肌缺血再灌损伤（I/R）的病理核心，为目前防治 I/R的焦点。团队前期研究证实，线粒体自噬是 I/R 微循环破坏重要特征，且人参三七药对（Rg1-R1）具有维持线粒体结构与功能，改善 I/R 效应，但其抗 I/R 作用机制不明。新近研究显示，FUNDC1 介导的线粒体自噬在心肌微循环再灌注损伤中发挥重要作用。据此假设：Rg1-R1 组分可通过调控缺血再灌内皮细胞 FUNDC1 介导的线粒体自噬，维持线粒体稳态，改善心肌微循环，减轻 I/R 损伤。为此，本课题拟采用 I/R 小鼠模型，首先研究 Rg1-R1 组分对小鼠心肌微循环舒张功能、屏障功能、管腔结构、线粒体自噬及相关分子的作用；进而敲低/过表达小鼠内皮细胞 FUNDC1，旨在揭示 Rg1-R1 组分通过调控 FUNDC1 介导的线粒体自噬以防治缺血再灌注损伤机制，为临床预防干预提供理论依据。

Myocardial microcirculation destruction is the pathological core of myocardial ischemia-reperfusion injury (I / R), and it is the focus of prevention and treatment of I / R at present. Earlier research by the team confirmed that mitochondrial autophagy is an important feature of I / R microcirculation disruption, and the Rg1-R1 has the ability to maintain mitochondrial structure and function and improve I / R effects, but its anti-I / R mechanism of action unknown. Recent studies have shown that FUNDC1-mediated mitochondrial autophagy plays an important role in myocardial microcirculation reperfusion injury. Based on this hypothesis: Rg1-R1 components can regulate mitochondrial autophagy mediated by ischemia-reperfusion endothelial cells FUNDC1, maintain mitochondrial homeostasis, improve myocardial microcirculation, and reduce I / R damage. To this end, this project intends to use the I / R mouse model to first study the role of Rg1-R1 components on the myocardial microcirculation diastolic function, barrier function, luminal structure, mitochondrial autophagy and related molecules in mice; The overexpression of mouse endothelial cells FUNDC1 is intended to reveal that Rg1-R1 components can prevent ischemia-reperfusion injury by regulating FUNDC1-mediated mitochondrial autophagy, and provide theoretical basis for clinical preventive intervention.