新研究表明瓣膜间质细胞行为改变是贯穿主动脉瓣钙化(AVC)进展的中轴线，并明确活性氧簇(ROS)是AVC始发因素。前期,我们证实miR-30b/133a1是稳定瓣膜间质细胞生理行为的精密调节器，其表达受ROS和Oct1的调控，而ROS又负调控Oct1的表达,据此我们提出"ROS/Oct1/miR-30b-133a1级联调控"假说，并推测该通路是促进AVC进展的推进器。为验证这一假说，我们将以瓣膜间质细胞为载体，逐步分析ROS对Oct1、Oct1对miR-30b/133a1的转录调控作用和机制;并以此为基础，考察Oct1是否介导ROS对miR-30b/133a1的表达调控；此外，构建体内外模型，进一步明确ROS/Oct1对AVC进展的促进作用。通过此研究，力图阐明导致miR-30b/133a1表达下调的机制及ROS/Oct1对AVC进展的作用，为"miRNA自身表达调控机制"研究提供新模型。

Recent studies have demonstrated that the phenotypic and functional changes of valvular interstitial cells were ongoing throughout AVC progression, and reactive oxygen species (ROS) was the original factor for AVC pathogenesis. Our preliminary findings showed that miR-30b/133a1 had the ability to regulate the phenotypic and functional changes of valvular interstitial cells, the expression of these two miRNAs were downregulated by ROS and Oct1, and Oct1 also decreased Oct1 expression. Accordingly, we proposed a hypothesis for "cascade regulation of ROS/Oct1/miR -30b-133a1" and speculated that this pathway is the promoptor for AVC progrssion. To test this hypothesis, we will take valvular interstitial cells as the carrier, and explore, step by step, the transcriptional regulation mechanism of ROS on Oct1, and Oct1 on miR-30b/133a1; based on the above findings, we will examine whether Oct1 mediates the regulation of miR-30b/133a1 by ROS; additionally, by using in vitro and in vivo model, we will investigate the role of ROS/Oct1 on valvular fibrosis and calcification. Through this research, we try to clarify the mechanisms to regulate the expression of miR-30b/133a1, and the effect of ROS/Oct1 on AVC progression, and construct a new model for "miRNA expression regulation" research.