ASPP1通过p53调控心肌缺血再灌注损伤

心肌缺血再灌注损伤是以心肌细胞损伤为特点的病理改变，目前仍缺乏有效的治疗药物，其机制有待进一步阐明。P53凋亡刺激蛋白1（ASPP1）是调节肿瘤细胞凋亡的重要蛋白，但其在心脏疾病中的作用仍不清楚。我们前期研究发现：1）ASPP1在心肌缺血再灌注损伤后表达升高。2）在过表达转基因小鼠，ASPP1促进心肌缺血再灌注损伤；而敲减ASPP1减轻了H/R对心肌细胞的损伤。3）心肌细胞在H/R损伤后，ASPP1与p53结合增加。4）LncRNA-812能够与ASPP1结合，进而影响ASPP1与p53功能复合物的形成。因此，我们假设：ASPP1通过与p53结合，增加p53对促凋亡基因的转录，诱导心肌细胞凋亡，调节心肌缺血再灌注损伤，这一过程受lncRNA-812调控。我们将应用基因过表达/敲除动物，结合分子生物学技术，阐明ASPP1和lncRNA-812在心肌缺血再灌注损伤中的作用与分子机制。

Myocardial ischemia-reperfusion (I/R) injury is a pathological change characterized by cardiomyocyte injury. Currently, there is still a lack of effective drug for I/R injury, and the underlying mechanism needs to be further elucidated. Apoptosis stimulating protein of p53-1 (ASPP1) is an important regulator of tumor cell apoptosis, but its role in heart disease is still unclear. Our previous results showed that: 1) ASPP1 expression was increased after myocardial I/R injury. 2) ASPP1 overexpression promoted I/R injury in transgenic mice, while ASPP1 knockdown attenuated H/R-induced cardiomyocyte injury. 3) Binding of ASPP1 and p53 was increased in cardiomyocytes following H/R injury. 4) Binding of lncRNA-812 to ASPP1 affected the formation of functional complex of ASPP1 and p53. Therefore, we hypothesized that binding of ASPP1 to p53 promotes transcription of p53-related pro-apoptotic genes, induces cardiomyocyte apoptosis, and regulates myocardial I/R injury; the process is regulated by lncRNA-812. Transgenic/knockout mice and molecular biology techniques will be used to clarify the role and molecular mechanism of ASPP1 and lncRNA-812 in myocardial I/R injury.