急性心肌梗死(AMI)是全球范围内严重危害人类健康的重要疾病之一。前期研究发现，自噬在AMI后早期被迅速激活，但自噬底物P62随缺血时间延长发生堆积，提示自噬流在AMI 中后期受损。损伤调节自噬调控基因1(DRAM1)是 p53下游的溶酶体膜蛋白。预实验表明，DRAM1在AMI小鼠心梗周边区表达明显增高；在心肌细胞中过表达DRAM1缓解长时缺氧引起的P62堆积并明显减轻心肌细胞凋亡。鉴于此，我们提出设想：DRAM1可改善缺血后心肌细胞自噬流，从而减少心肌细胞凋亡、逆转AMI心肌重构。为证明这一猜想，拟在实验性小鼠AMI模型中研究DRAM1对AMI后心脏功能及心肌重构的影响并探讨其作用是否依赖于自噬流；并从细胞和分子水平研究DRAM1与自噬相关蛋白及溶酶体功能蛋白是否存在相互作用，以期明确DRAM1改善自噬流、影响AMI心脏预后的分子机制。本研究将揭示改善心肌缺血后自噬流受损的新机制。

Acute myocardial infarction (AMI) is one of the most common heart diseases that cause morbidity and mortality worldwide. Our previous studies have shown that autophagy was activated quickly after AMI, and however, autophagy substrate P62 began to accumulate along with the prolonged ischemia. Our results indicated that autophagy flux was impaired in the latter phase of the AMI. The damage-regulated autophagy modulator 1 (DRAM1), a novel P53 target gene, is a lysosomal protein and has been reported to be essential in P53-dependent autophagy activation and apoptosis. The preliminary data showed that DRAM1 expression was upregulated in the infarct border zone of the AMI mice. Overexpression of DRAM1 in the cardiomycytes alleviated P62 accumulation and cell apoptosis caused by hypoxia significantly. On the basis of the literature and the preliminary data we proposed the hypothesis: DRAM1 will improve cardiomycyte autophagy flux and reduce cell apoptosis after ischemia by promoting autophagy-lysosome degradation pathway. To address this issue, we will use the mouse acute myocardial infarction model in vivo and H9C2 cells oxygen glucose deprivation model in vitro, first observing the effect of DRAM1 in the hearts of AMI and then exploring the mechanism by which DRAM1 improve the impaired autophagy flux after AMI. Our study will provide a strong rationale for developing the novel mechanism and approach to effectively improve the prognosis of AMI.