抗菌肽CRAMP保护心肌缺血再灌注损伤及其分子机制研究

Cathelicidin-related antimicrobial peptide (CRAMP) controls immune and inflammatory reactions, and is associated with cell apoptosis. Myocardial ischemia-reperfusion injury (IRI) induces oxidative stress and inflammatory infiltration, leading to enhanced cardiomyocyte apoptosis and necrosis. However, the role of CRAMP in myocardial IRI remains unclear. Our preliminary data indicate that CRAMP could be induced in hydrogen peroxide (H2O2)-treated H9C2 cardiomyocytes mimicking myocardial IRI in vitro. CRAMP was found to be able to reduce H2O2-induced apoptosis in cardiomyocytes, indicating that CRAMP might be protective for myocardial IRI. In this project, based on H9C2 cell line (treated with H2O2) and primary isolated of cardiomyocytes (treated with oxygen-glucose deprivation/reperfusion), as well as using murine model of myocardial IRI by coronary artery constriction, we will perform gain- and loss-of function assays to clarify the role of CRAMP in myocardial IRI. Furthermore, based on the identified downstream targets of CRAMP using bio-informatics analysis, we will perform rescue assays to reveal the molecular basis of CRAMP in the control of myocardial IRI. CRAMP might be a novel target for myocardial IRI treatment.

抗菌肽CRAMP参与调控免疫、炎症反应，影响细胞凋亡。心肌缺血再灌注损伤（ischemia-reperfusion injury，IRI）时，心脏遭受氧化应激及炎症刺激，加重心肌细胞的凋亡和坏死，然而CRAMP在心肌IRI中的作用尚未明确。我们在前期运用过氧化氢（H2O2）刺激H9C2心肌细胞系，CRAMP在体外模拟的IRI模型中被诱导表达，而CRAMP预处理可显著降低H2O2诱导的心肌细胞凋亡，提示干预CRAMP可能可以防治心肌IRI。在本项目中，我们拟基于大鼠H9C2心肌细胞（H2O2刺激）和原代心肌细胞（缺氧复氧实验），或基于冠状动脉结扎术诱导IRI的小鼠模型，行CRAMP功能获得性和缺失性实验，明确CRAMP与心肌IRI的关系。进一步基于生物信息学预测的CRAMP下游调控分子，行功能挽救实验，明确CRAMP保护心肌IRI的分子机制。干预CRAMP有望成为防治心肌IRI的新策略。

抗菌肽CRAMP参与调控免疫、炎症反应，影响细胞凋亡。心肌缺血再灌注损伤（ischemia-reperfusion injury，IRI）时，心脏遭受氧化应激及炎症刺激，加重心肌细胞的凋亡和坏死，然而CRAMP在心肌IRI中的作用尚未明确。在本项目中，我们基于原代心肌细胞（缺氧复氧实验），或基于冠状动脉结扎术诱导IRI的小鼠模型，行CRAMP功能获得性和缺失性实验，明确CRAMP与心肌IRI的关系。进一步基于生物信息学预测的CRAMP下游调控分子，行功能挽救实验，明确了CRAMP保护心肌IRI的分子机制。明确了干预CRAMP有望成为防治心肌IRI的新策略。