转录因子CREB1通过lncRNA Pvt1调控c-Myc/p53凋亡相关通路在脓毒性休克大鼠心肌抑制中作用机制的研究

心肌抑制是导致脓毒性休克不良预后的重要因素。已知长链非编码RNA在细胞信号通路的调控中具有重要的作用，但lncRNA在脓毒症心肌抑制中的作用目前尚不明确。我们前期研究发现，脓毒症心肌抑制模型中lncRNA Pvt1显著升高，细胞水平预实验提示可以改善凋亡，同时发现转录因子CREB1的表达量显著升高，且生物信息学预测发现CREB1可以调控Pvt1基因的表达，并可能通过靶基因c-Myc及p53参与细胞凋亡的调控。据此，我们提出假说：CREB1启动Pvt1基因的转录，使lncRNA Pvt1表达量增加，通过调控c-Myc以及p53影响心肌细胞凋亡进而影响心功能。本课题拟从分子、细胞、组织以及动物多层次明确CREB1调控lncRNA Pvt1参与凋亡通路在脓毒症心肌抑制中的作用，从lncRNA这个新视点探讨脓毒症心肌抑制的发病机制，为临床治疗提供新思路。

Long non-coding RNA plays a critical role during the process of cell apoptosis. However, the relationship between lncRNA and sepsis-induced myocardial depression is still unclear. Our previous study showed that the expression level of lncRNA Pvt1 in heart tissue was higher in the animal group of sepsis-induced myocardial depression. Additionally, through bioinformatic prediction, we found that the CREB1 transcription factor could regulate the expression of Pvt1 gene, increase the expression of lncRNA Pvt1, and then might influence the c-Myc as well as p53 gene, which really matter in the regulation process of cell apoptosis. Therefore, we recognized that lncRNA Pvt1 made sense in sepsis-induced myocardial depression. Besides, there were no studies representing the aforementioned association. Considering all these facts, we suppose that CREB1 transcription factor could generate the Pvt1 gene expression, and lncRNA Pvt1 could regulate c-Myc and p53 gene expression and influence the cell apoptosis in sepsis-induced myocardial depression. Our study will elucidate the function of lncRNA Pvt1 in the molecular, cell, tissue, and animal levels. Furthermore, we hope our study could figure out that CREB1 could regulate Pvt1 gene, make sure lncRNA Pvt1 might influence the c-Myc and p53 target gene, and finally have an impact in heart function. With the in-depth understanding of the mechanism of sepsis, non-coding RNAs provide a new insight into sepsis and could become the novel therapeutic targets in the future.