导致心力衰竭的分子发病机理至今尚未完全阐明，严重制约对心衰的预防和治疗。目前认为心衰是由多因素参与，并经多信号转导通路介导，其中蛋白激酶C (PKC) 信号通路尤为重要。但PKC是如何促进心衰发生发展的分子机制仍不明朗。申请人曾发现PKC增强半乳凝集素-3 (Galectin-3) 诱导的心肌纤维化(BBA,2015)。最近我们新发现PKC是通过促进Src激酶来调节Galectin-3的表达。因此，我们提出存在PKC-Src-Galectin-3通路，推测该通路活性增强在介导心衰发生发展过程中起着非常重要的作用。本课题拟从体外和体内两方面, 采用分子生物学、 基因转染、 siRNA基因敲除和超高速离心等实验技术，以Galectin-3为切入点, 在分子水平探讨PKC-Src-Galectin-3这一新机制在介导心衰发病过程中的作用, 为揭示心力衰竭的发病机理提供新的理论。

Protein kinase C (PKC) and PKC activated pathways play an important role in the pathogenesis of heart failure. However, the underlying molecular mechanisms and signaling pathways are not fully understood. We recently reported that PKC upregulates galectin-3 expression and promotes cardiac fibrosis (published in BBA Molecular Cell Research, 2015). We have new data showing that PKC stimulates Src kinase and subsequently increases galectin-3 expression. We therefore propose that the activation of PKC-Src-Galectin-3 pathway may play a key role in heart failure development. To achieve our goal, a combination of molecular biology, gene transfection, siRNA knockdown，sucrose gradient ultracentrifugation, etc will be employed in both cultured mouse HL-1 cardiomyocytes and a pulmonary artery banding (PAB)-induced heart failure animal model. The success of this project will provide new insight into heart failure development and rationale for potential therapeutic intervention fighting against this devastating disease.