“冬眠诱导因子”及lncRNA Tug1/miR-223 crosstalk信号通路在深低温停循环脑保护的应用机制研究

冬眠是冬眠物种在资源匮乏时期抵抗缺血缺氧再灌注损伤的重要生存策略，可以有效的抵抗脑、心脏等多脏器深低温低灌注导致的器官损伤。DHCA是临床治疗主动脉弓部病变及复杂先心病常用的技术手段。脑损伤仍是DHCA的重要并发症。冬眠物种体内存在的冬眠诱导因子（HIT）可以被诱导提纯，并发挥抵抗DHCA脑损伤的作用。然而，其确切结构及氨基酸序列仍不明确。lncRNATug1是目前确认的与冬眠发生相关的非编码RNA，在脑中高度表达。HIT是否可通过调控lncRNATug1发挥神经保护作用需要进一步实验研究。生物信息学预测及相关文献认为lncRNATug1可与miR-223相互调控，发挥神经保护作用。本课题拟采用已建立的冬眠金花松鼠模型提纯HIT，进行后续鉴定验证，建立大鼠DHCA模型，系统评价HIT及靶向调控lncRNA Tug1/miR-223的神经保护作用，为临床DHCA脑保护提供新的治疗选择。

Hibernation is an important survival strategy for hibernating species against ischemia, hypoxia and reperfusion injury when resources are scarce. It is effective against organ damage caused by deep hypothermia and hypoperfusion in the brain, heart and other organs. DHCA is a commonly used technique for clinical treatment of aortic arch diseases and complex congenital heart disease. Brain injury remains an important complication of DHCA. The hibernation-inducing tigger (HIT) present in hibernating species can be induced and purified. HIT can play a role in protection of brain. However, its exact structure and amino acid sequence remains unclear. lncRNA Tug1 is currently recognized as a non-coding RNA associated with hibernation and is highly expressed in the brain. Whether HIT can exert neuroprotective effects by modulating lncRNA Tug1 requires further experimental studies. lncRNA Tug1/miR-223 crosstalk is predicted to exert neuroprotective effects from bioinformatics predictions and related literature. The aim of this study was to purify HIT from the established hibernating chipmunks for subsequent identification and validation, establish a rat DHCA model, systematically evaluate the neuroprotective effect of HIT and target the regulation of lncRNA Tug1 / miR-223, and provide a new treatment for brain protection during DHCA.