LncRNA MIAT调控Cryab参与深低温低流量后脑缺血再灌注损伤

深低温低流量(DHLF)后脑缺血再灌注损伤是目前复杂先心病体外循环术后亟待解决的问题。新近研究表明LncRNA在神经系统损伤中发挥着重要作用。本课题组首次利用LncRNA测序发现，LncRNA MIAT(MIAT)高表达于DHLF后的大脑皮层，文献报道MIAT广泛参与凋亡调控，而神经元凋亡是DHLF后脑损伤的主要表现，提示MIAT可能参与DHLF后脑缺血再灌注损伤。通过生物信息学分析及预实验发现Cryab可能为MIAT的关键靶点，有研究显示Cryab在抗凋亡中起重要作用。据此推测：LncRNA MIAT通过调控Cryab基因参与DHLF后脑缺血再灌注损伤。课题组拟建立小鼠DHLF细胞及动物模型，采用过表达与沉默策略，结合RIP和RNA拉下实验，验证MIAT和Cryab相互调控关系，阐明其在DHLF后脑缺血再灌注损伤中的作用，为开发DHLF脑保护策略提供新的理论依据。

Cerebral ischemia-reperfusion injury after deep hypothermic low flow(DHLF) is an urgent issue for complex congenital heart disease surgery. Recent studies have shown that LncRNA plays an important role in neurological damage. In this study, LncRNA sequencing showed that LncRNA MIAT(MIAT) was highly expressed in the cerebral cortex after DHLF. MIAT was widely involved in the regulation of apoptosis, and neuronal apoptosis was the main manifestation of brain injury after DHLF, suggesting that MIAT may be involved in cerebral ischemia-reperfusion injury after DHLF. Bioinformatics analysis and pre-experimentation showed Cryab was the key target of MIAT. Meanwhile, Cryab plays an important role in anti-apoptosis. Accordingly, we hypothesized that LncRNA MIAT regulates Cryab gene to involve in cerebral ischemia-reperfusion injury after DHLF. In this study, we planned to build the DHLF cell and animal models. The overexpression and silencing strategies were used. The relationship between MIAT and Cryab was verified by RIP and RNA pull-down assay, which can explain the mechanism of cerebral ischemia-reperfusion injury after DHLF. The solution of this scientific problem will provide a new theoretical basis for brain protection strategy after DHLF.