控制心肌肥厚发生发展的中心环节是相关基因转录调控，蛋白质转录因子间相互作用及表观遗传机制为机体提供了精细的转录控制。Myocardin是血清反应因子（SRF）强力辅助因子，激活肥厚标志基因其表达，触发心肌肥厚。神经限制性沉默因子（NRSF）负性调控肥厚基因表达。我们前期证明NRSF抑制Myocardin诱导心肌肥厚，本研究在此基础上，将利用细胞和分子生物学技术，阐明NRSF抑制Myocardin介导心肌肥厚机制，包括二者蛋白相互作用，降低myocardin与SRF结合,减弱其对肥厚基因转录激活；抑制组蛋白乙酰化；对组蛋白相同位点赖氨酸甲基化或乙酰化修饰产生相反效应等。同时，利用转基因小鼠，证明NRSF抑制myocardin触发的心肌肥厚及上述机制。总之，本研究在分子-细胞-整体水平，证明NRSF.抑制Myocardin触发的心肌肥厚及上述机制，为心肌肥厚防治提供新的理论依据。

Transcriptional regulation of the genes to control cardiac hypertrophy is one of the most important mechanisms of hypertrophic development. Interactions of protein-protein among transcriptional factors and secondary epigenetic changes provide perfectly gene transcriptional control. Myocardin is a serum response factor (SRF) powerful co-transcriptional factor, which activates the expression of hypertrophic marker genes and then triggers myocardial hypertrophy. Neuronal restrictive silencer factor (NRSF) can negatively regulate hypertrophic genes. Our previous studies have demonstrated that NRSF can inhibit myocardin- induced myocardial hypertrophy. On the basis of this, it will be investigated the related mechanisms that NRSF inhibits the cardiac hypertrophy by cellular and molecular biology technology. These mechanisms will include the two protein interaction and thus reduce myocardin and SRF binding to weaken the activation of hypertrophic gene transcription. Furthermore, it will also be investigated that the exchanges of histone acetylation/ deacetylation and the same site of lysine methylation or acetylation on histone could be caused by them. At the same time, related transgenic mice will be used in this study to demonstrate that NRSF inhibits myocardin triggering myocardial hypertrophy and the mechanisms. In conclusion, this study will provide the novel evidence and mechanism that NRSF negatively regulates myocardial hypertrophy to be triggered by myocardin activation and the mechanism, new theoretical basis for prevention and treatment of myocardial hypertrophy as well.