miR-30c调控Sox9-NF-κB通路对心肌缺血-再灌注损伤的作用及机制研究

Myocardial Ischemia-Reperfusion Injury (MIRI) during cardiac surgery severely affects the recovery of cardiac function, so it is important to reduce MIRI. Previous studies found that miR-30c expression was reduced in MIRI, but its role was unknown. miR-30c is highly expressed in the heart. Sox9 is one of miR-30c target genes. The up-regulation of miR-30c can inhibit the expression of Sox9, and it can also negatively regulate the NF-κB pathway to reduce the inflammatory response and apoptosis. And Sox9 may be the regulatory center of NF-κB. Therefore, we hypothesized that up-regulation of miR-30c regulates the Sox9-NF-κB pathway to mitigate MIRI. Therefore, this project intends to establish a model of cardiopulmonary ischemia-reperfusion and cardiomyocyte hypoxia-reoxygenation in adult rats. Using transgenic, viral transfection, and gene silencing techniques to measure cardiac function, inflammation and apoptosis-related markers, including the Sox9-NF-κB pathway related indicators to clarify the role of miR-30c in reducing MIRI and its relationship with Sox9-NF-κB signaling pathway, in order to provide a new theoretical basis and strategy for the prevention and treatment of clinical MIRI.

心脏手术中发生心肌缺血-再灌注损伤（MIRI）严重影响心功能恢复，因此减轻MIRI十分重要。前期研究发现 miR-30c 在缺血再灌注损伤心肌中表达降低，但其作用不明。miR-30c在心脏中高表达，Sox9作为miR-30c靶基因之一，miR-30c表达上调可抑制Sox9的表达，也可负向调控NF-κB通路以减轻细胞炎症反应及凋亡。且Sox9可能是NF-κB调控中枢。那么，我们设想上调miR-30c表达可调控Sox9-NF-κB通路起到减轻MIRI作用。因此，本项目拟建立成年大鼠体外循环心脏缺血-再灌注与心肌细胞缺氧-复氧模型，采用转基因、病毒转染及基因沉默等技术，通过测定心功能，检测炎症、凋亡相关指标和Sox9-NF-κB相关指标，明确 miR-30c 在减轻 MIRI 中的作用及其与Sox9-NF-κB信号通路的关系，以期为临床MIRI的防治提供新的理论依据和策略。

心脏手术中发生心肌缺血-再灌注损伤（MIRI）严重影响心功能恢复，因此减轻MIRI十分重要。前期研究发现miR-30c在缺血再灌注损伤心肌中表达降低，但其作用不明。miR-30c在心脏中高表达，Sox9作为miR-30c靶基因之一，miR-30c表达上调可抑制Sox9的表达，也可负向调控NF-κB通路以减轻细胞炎症反应及凋亡。且Sox9可能是NF-κB调控中枢。那么，我们设想上调miR-30c表达可调控Sox9-NF-κB通路起到减轻MIRI作用。因此，本项目拟建立成年大鼠体外循环心脏缺血-再灌注与心肌细胞缺氧-复氧模型，采用转基因、病毒转染及基因沉默等技术，通过测定心功能，检测炎症、凋亡相关指标和Sox9-NF-κB相关指标，明确miR-30c在减轻MIRI中的作用及其与Sox9-NF-κB信号通路的关系，以期为临床MIRI的防治提供新的理论依据和策略。研究结果表明：细胞水平： I/R大鼠的miR-30c被大大下调，可以直接靶向SOX9。此外，miR-30c可作为细胞焦亡的抑制因子，以对抗I / R诱导的心脏疾病。大体水平：（1）miR-30c在CPB下MI/RI的大鼠心肌组织中表达降低。（2）过表达miR-30c可抑制CPB下MI/RI大鼠心肌组织NF-κB的激活，减少心肌细胞凋亡，减轻大鼠的心肌损伤，具有心肌保护作用。（3）NF-κB激活剂BA可减弱miR-30c的心肌保护作用，NF-κB/Bcl-2通路参与miR-30c的心肌保护过程。