研究发现Notch通路不仅调节炎症性疾病，而且参与高血压心肌纤维化过程，已证实炎症可以导致心肌纤维化，那么Notch通路是炎症导致心肌纤维化的信号转导通路之一吗？预实验发现Notch1+/-小鼠在血管紧张素II(Ang II)刺激后，心肌组织中IL-1β和TNF-ɑ的mRNA水平、纤维素沉积和TGF-β表达均明显比WT小鼠低。提示Notch1通路可能通过调节炎症反应参与心肌纤维化的发生发展。本课题拟在体外心肌成纤维细胞、Notch1+/-小鼠、WT小鼠，用抑制剂DAPT和激动剂Jagged1预处理，再用Ang II诱导心肌纤维化，研究Notch1通路与炎症在心肌纤维化中的相互作用，以明确Notch1信号是通过调节炎症反应参与心肌纤维化过程。如证明Notch1信号是炎症导致心肌纤维化的信号通路之一，将为高血压心肌重塑发病机制提供新的理论依据，提示调节Notch通路可能是治疗该疾病的新靶点。

Recent findings have demonstrated a critical role of Notch signal pathway not only in the inflammatory diseases, but also in the adult myocardial diseases such as myocardiac fibrosis. It is known that inflammation can lead to myocardiac fibrosis, and then, would the Notch pathway be a regulatory signal of myocardiac fibrosis induced by inflammation？Our preliminary study found that cardiac hypertrophy by Angiotensin II infusion caused lower mRNA levels of IL-1 and TNF-ɑ in myocardial tissue of Notch1+/- mice than that of WT mice, in addition cellulose deposition and TGF-β express were the same tendency. Therefore, we have a hypothesis that the Notch1 pathway involved in the myocardiac fibrosis by regulated the inflammatory reaction. In the present study, using primary cardiomyocytes pretreated with DAPT, a Notch signal inhibitor, and with Jagged1, a Notch signal agonist, Notch1+/- mice and WT mice Ang II-induced myocardial fibrosis, first we want to study the changes of Notch pathway and inflammatory factor, and their relationships；second, we want to study the inflammatory response and myocardial fibrosis, when the Notch signal be inhibited and activated. This subject is put forward for that the Notch1 signal regulated the inflammatory response in the development of myocardial fibrosis, and suggest that it may be a potential therapeutic target for the treatment of cardiac hypertrophy and heart failure.