Notch3介导RhoA_ROCK_Hif1_轴对心肌梗死心功能的影响.pdfVIP

Notch3介导RhoA/ROCK/Hif1α轴对心肌梗死心功能的影响 【摘要 】目的 分析Notch3介导RhoA/ROCK/Hif1α轴对心肌梗死（MI）心功能的影响。方法 将45 只雄性SD大鼠随机分为假手术组、模型组和Notch3过表达组三组，每组各15只。大鼠心肌注射Notch3 慢病毒过表达后构建MI模型。术后12周检测心功能及心脏血流动力学指标，观察心肌组织结构，并检 测心肌组织Notch3和RhoA/ROCK/Hif1α轴相关蛋白水平。结果 与假手术组比较，模型组大鼠心肌组织 Notch3表达水平、左心室射血分数（LVEF）、左心室舒张末压（LVEDP）显著降低，左心室收缩末期内 径（LVESD）、左心室舒张末期内径（LVEDD）、左心室收缩末压（LVESP）、左心室压力最大上升速 率（LV+dp/dtmax）、左心室压力最大下降速率（LV-dp/dtmax）、心肌组织RhoA、ROCK1、ROCK2、 Hif1α表达水平显著增加（P ＜0.05）；Notch3过表达组大鼠LVESD和LVEDD显著小于模型组，心肌组织 Notch3表达水平、LVEF、LVEDP显著高于模型组（P ＜0.05）；LVESP、LV+dp/dtmax和LV-dp/dtmax、 心肌组织RhoA、ROCK1、ROCK2、Hif1α表达水平显著降低（P ＜0.05）。结论 Notch3过表达可能通过 RhoA/ROCK/Hif1α轴抑制MI后心肌代偿性肥厚，逆转左心室扩大，改善心功能。 【关键词 】Notch3；RhoA/ROCK/Hif1α轴；心肌梗死；血流动力学；大鼠 [Abstract] Objective To analyze the influence of Notch3-mediated RhoA/ROCK/Hif1α axis on heart function in myocardial infarction (MI). Methods Male SD rats (n=45) were divided randomly into sham-operation group, model group and Notch3 over-expression group (each n=15). MI model was established by injecting Notch3 lentivirus into rat myocardium after over expression. The indexes of heart function and cardiac hemodynamics were detected and myocardial tissue structure was observed after 12 weeks. The levels of myocardial Notch3 and RhoA/ROCK/Hif1α axis related proteins were detected. Results Compared with sham-operation group, Notch3 expression level, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP) decreased significantly, and left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic inner diameter (LVEDD), left ventricular end-systolic pressure (LVESP), the maximal ascending velocity of left ventricular pressure (LV+dp/dtmax), the maximal descending velocity of left ventricular pressure (