心脏成纤维细胞向肌成纤维细胞转化是心脏间质重塑的关键节点，补体C1q/TNF相关蛋白家族成员CTRP6对其影响尚无报道。本课题拟在大鼠心肌梗死模型检测纤维化进程中CTRP6的变化；观察心脏局部过表达CTRP6对心脏肌成纤维细胞转化及间质纤维化的影响，在整体水平上明确CTRP6对间质重塑的作用。在离体培养的成年大鼠心脏成纤维细胞上，采用Real-time PCR、免疫印迹和免疫荧光等方法观察CTRP6对肌成纤维细胞转化和细胞外基质合成的影响；采用工具药、RNA干扰、质粒转染、免疫共沉淀以及荧光素酶报告基因检测等方法，从受体、胞内蛋白激酶、转录因子层面探讨CTRP6调控肌成纤维细胞转化的信号转导通路，明确AMPK以及血清反应因子的共转录激活因子MRTF-A在CTRP6抑制肌成纤维细胞转化中的关键作用和转录调控机制。这将为阐明CTRP6的生物学作用提供新见解，也为防治心脏间质重塑提供新思路。

The transformation of cardiac fibroblast to myofibroblast is principle for the interstitial remodeling after myocardial infarction (MI). Little is known about the effect of C1q TNF-related protein (CTRP)-6, a member of the CTRP family, on myofibroblast transformation and cardiac fibrosis. This study will investigate the alteration of CTRP6 expression in rats with cardiac fibrosis undergoing MI and observe the effect of CTRP6 over-expression in heart on myofibroblast transformation and interstitial fibrosis. In cultured adult rat cardiac fibroblast, we will explore the effect of CTRP6 on myofibroblast transformation and collagen production by use of methods including Real-time PCR, Western blot, immunofluorescent staining, and etc. The signal transduction mechanism involved in CTRP-6-modulated myofibroblast transformation will be revealed from receptor, intracellular protein kinase, and transcription factor levels by using pharmacological inhibitors, RNA interference, plasmid transfection, immunoprecipitation, and luciferase assay system. This study will clarify the key role of AMP-activated protein kinase (AMPK) and myocardin-related transcription factor A (MRTF-A), a serum response factor (SRF) co-activator, in controlling myofibroblast transformation. This study will provide a novle insight into the biological effect of CTRP6 and offer a new therapeutic target for preventing and treating myocardial interstitial remodeling.