心肌成纤维细胞（CFs）活化在心肌纤维化中作用关键。糖酵解可活化CFs并促进心肌纤维化；线粒体分裂可促进糖酵解而动力相关蛋白1（Drp1）是引起线粒体分裂最重要因素。生物信息学分析显示LncRNA Dnm3os在缺血性心肌病心肌组织中显著升高；预实验结果显示siRNA- Dnm3os抑制CFs活化、糖酵解、线粒体分裂和Drp1。Drp1可能受H3K9乙酰化和CaMKII调控；而Dnm3os又可以促进H3K9乙酰化并激活CaMKII。结合上述，我们提出以下科学问题：①Dnm3os是否在心肌纤维化发生起重要作用；②上调糖酵解是否Dnm3os调控纤维化主要机制；③Dnm3os是否通过Drp1引起过度线粒体分裂并促进糖酵解；④Dnm3os是否通过H3K9乙酰化和CaMKII激活调控Drp1。围绕科学问题，本项目将着眼于CFs糖酵解，阐明Dnm3os对心肌纤维化的作用和机制，为临床防治提供更多思路。

The activation of cardiac fibroblasts (CFs) plays a key role in cardiac fibrosis. Glycolysis activates CFs and promotes cardiac fibrosis. Mitochondrial fission, which is mediated by dynamin-related protein 1 (Drp1), promotes glycolysis. Bioinformatics analysis showed that LncRNA Dnm3os was significantly elevated in myocardial tissue of ischemic cardiomyopathy. Preliminary results showed that siRNA-Dnm3os inhibited CFs activation, glycolysis, mitochondrial fission and Drp1 expression. Binding sites of acetylated-H3K9 in the promoter region of Drp1 are predicted and Drp1 Ser616 phosphorylation, which facilitates Drp1 translocating to mitochondria and leads to mitochondria fission, is promoted by CaMKII. Interestingly, Dnm3os is found to induce H3K9 acetylation and activates Ca2+ signal. We thus propose scientific problems: 1. Does Dnm3os play an important role in cardiac fibrosis? 2. Is glycolysis induced by Dnm3os essential for Dnm3os-induced cardiac fibrosis? 3. Is mitochondrial fission caused by Dnm3os improtant in Dnm3os-induced fibrosis? 4. Does Dnm3os promote Drp1 transcription by increasing H3K9 acetylation and induce Drp1 Ser616 phosphorylation via activation of CaMKII? To solve these problem, the current project aims to focus on CFs glycolysis, clarifying the roles and mechanisms of Dnm3os on cardiac fibrosis.