心肌纤维化发生机制复杂，目前的治疗药物针对性不强且副作用较大。TGF-β1作为一种强效的致纤维化因子，在心肌纤维化的发生中起着重要作用，而TGF-β/Smads信号通路是TGF-β1发挥生物学作用的主要通路。蛇床子素是一种毒副作用小的烃基香豆素类单体化合物，我们前期的研究首次发现其新的药理作用- - 抗心肌纤维化，且其作用机制与降低TGF-β1的表达有关。为了进一步明确其作用机制，本课题首先以TGF-β1转基因小鼠为研究对象，观察蛇床子素对TGF-β/Smads信号通路的影响，然后在细胞实验中加入 TβRⅠ胞内激酶抑制剂和TGF-β1，进一步观察蛇床子素对原代培养的心肌成纤维细胞TGF-β/Smads信号通路的影响。通过正反论证，从动物、组织、细胞、分子水平阐明蛇床子素抗心肌纤维化的作用机制是否与TGF-β/Smads通路有关，为我国寻找一种确实有效且毒副作用低的抗心肌纤维化药物提供新的策略。

The pathogenesis of myocardial fibrosis is complex and the current therapeutic drugs aren't targeted and have many side effects. TGF-β 1, as a strong factor leading to fibrosis, plays an important role in the myocardial fibrosis. It is well known that TGF-β1 exerts its biological effects by TGF-β/ Smads signal pathway. Osthole is a coumarin monomeric compound with low toxic effect. Our preliminary experiment first discovered that osthole could inhibit myocardial fibrosis and its possible mechanism might be related to the reduction of TGF-β1 expression. In order to further identify its mechanism,this project will use TGF-β 1 transgenic mice to observe the effect of osthole on TGF-β/Smads signal pathway. In the next cell experiment, TβRⅠ intracellular kinase inhibitor and TGF-β1 will be used in fibroblasts to observe the effect of osthole on TGF-β/Smads signal pathway. This project will elucidate whether the mechanism of osthole inhibiting myocardial fibrosis is associated with TGF-β/Smads signal pathway from animal,tissue,cell and molecular level. It will provide a new strategy for our country to find an effective and low toxic effect anti-myocardial fibrosis drug.