研究表明，TLR4/NF-κB信号通路在心肌梗死（MI）后心室重塑中呈现持续活化状态，参与心室重塑的发生发展，然其持续活化的机制尚未明确。miRNA在信号通路调控中扮演重要角色。我们的前期研究提示心室重塑时TLR4/NF-κB通路活化伴miR-27b表达上调。生物信息学分析提示，miR-27b的启动子区域具备NF-κB的结合位点，TLR4/NF-κB通路的负性调控因子PPAR-γ则很可能是miR-27b的作用靶点。因此，我们推测miR-27b是TLR4/NF-κB通路的"开关"，能启动正反馈效应导致其持续活化参与不良心室重塑。本课题拟动态观察MI后TLR4/NF-κB/miR-27b/PPAR-γ的变化及上调/下调miR-27b对TLR4/NF-κB /PPAR-γ和心室重塑的影响，以期验证以上假说。结果有助于阐明心室重塑中TLR4/NF-κB的激活及调控机制，为靶向干预提供新靶点。

Mounting evidence suggests that persistent activation of toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway which is triggered by the endogenous ligands contributed to the myocardial inflammation, adverse ventricular remodeling and the pathogenesis of heart failure. The mechanism which is responsible for the persistant activation of TLR4/NF-κB signaling pathway remains unclear. It has been recently demonstrated that microRNA (miRNA) play an essential role in the regulation of signaling pathways. Our pre-experimental study revealed that the activation of TLR4/NF-κB was accompanied by up-regualtion of miR-27b in the infarcted myocardium and LPS-stimulated cardiomyocytes. Bioinformatic analyses indicated that there is binding site for NF-κB in the promoter region of miR-27b and peroxisome proliferator-activated receptor gamma(PPAR-γ) which inhibited the TLR4/NF-κB pathway is the predicted target of miR-27b. Therefore, we hypothesized that a TLR4/NF-κB-miR-27b positive feedback loop is involved in the ventricular remodeling after myocardial infarction. To test the hypothesis, we plan to study the dynamics of TLR4/NF-κB/miR-27b/PPAR-γ after myocardial infarction and the effects of up-regulating or down-regulating miR-27b on TLR4/NF-κB/PPAR-γ and ventricular remodeling.Our study will clarify the mechanism for activation and regulation of TLR4/NF-κB signaling pathway in the ventricular remodeling and provide new target for intervention.