心脏纤维化是众多心血管疾病发生和发展的共同病理基础。Akp2由ALPL基因编码，是磷酸酶家族成员，但在心脏纤维化中的作用及机制尚无报道。本课题组发现Akp2与急性ST段抬高型心肌梗死患者院内累积死亡率显著相关。体内研究发现，抑制Akp2，心梗诱导的小鼠心脏纤维化显著改善；反之，过表达Akp2心脏纤维化加重。我们假设：Akp2可能具有促进心脏纤维化作用，抑制Akp2可能发挥抗心脏纤维化作用，其机制可能经过AMP-AMPK-P53通路介导。本研究将：①采用Akp2条件性敲除及慢病毒过表达等模型，探讨Akp2基因在心脏纤维化中的作用；②采用Akp2基因敲除和慢病毒过表达的原代CFs细胞模型，来探索Akp2对CFs分化、迁移、胶原相关基因及蛋白表达的影响；③研究Akp2是否通过AMP-AMPK-p53/p21通路调控心脏纤维化，从而阐明Akp2在心脏纤维化中作用的分子机制。

Cardiac fibrosis is the common pathological basis of many cardiovascular diseases. Akp2, encoded by the ALPL gene, is a member of the phosphatase family, but its role and mechanism in cardiac fibrosis has not been reported. We found that Akp2 was significantly associated with the in-hospital cumulative mortality in patients with ST-segment elevation myocardial infarction. In vivo study showed that inhibition of Akp2 significantly improved myocardial infarction-induced cardiac fibrosis in mice. Conversely, Akp2 overexpression exacerbated cardiac fibrosis. We hypothesized that Akp2 may promote cardiac fibrosis, and Akp2 inhibition may play an anti-cardiac fibrosis role, which may be mediated by the AMP-AMPK-p53 pathway. This study was conducted to investigate the role of Akp2 gene in cardiac fibrosis using Akp2 conditional knockout mice and lentivirus overexpression models. Primary CFs cell model with Akp2 gene knockout and lentivirus overexpression was used to explore the influence of Akp2 on CFs differentiation, migration, collagen-related genes and protein expression. And to investigate whether Akp2 regulates cardiac fibrosis through the AMP-AMPK-p53 pathway, so as to elucidate the molecular mechanism of Akp2 on cardiac fibrosis.