Akt3-Iws1通路在深低温低流量脑白质损伤中作用机制的研究

Deep hypothermic low flow（DHLF）cardiopulmonary bypass is one of the assistant techniques vital for congenital heart disease surgery. The neurological deficits seen in children after surgical correction may be attributed to the developing status of cerebral white matter, which is more susceptible to the ischemia-reperfusion injury after the long-term DHLF. Iws1, an RNA processing regulator, was identified as a substrate of Akt3 by phosphoproteomics screen. The established DHLF mouse model exhibited abnormal white matter development, along with the diminished Akt3-Iws1 signaling node. Gain- and loss-of-function will be assessed on In vitro and In vivo model. Molecular and cellular insights into Akt3-Iws1 signaling cascade in developmental and pathological conditions should provide promising therapeutic targets for cerebral white matter injuries after the long term DHLF.

深低温低流量(deep hypothermic low flow, DHLF)体外循环是先天性心脏病手术的重要辅助手段之一。先心病患儿正处于出生后脑白质发育的活跃期，对长时程DHLF缺血再灌注较为敏感，易引发脑白质损伤相关神经系统疾病。我们的预实验结果表明，RNA剪切调节蛋白Iws1受Akt3（蛋白激酶Bγ）磷酸化调控，并参与了长时程DHLF诱发的脑白质损伤的病理进程。Akt3在脑白质发育及稳定性维持方面的重要功能已得到广泛验证，但Iws1调控脑白质中少突胶质细胞谱系发育过程的细胞和分子机制尚不明确。我们将在分子、细胞和动物三个层次，从功能获得和缺失两个方面，研究Akt3-Iws1及其下游通路是如何介导长时程DHLF诱导的脑白质少突胶质细胞谱系发育异常的，这将为治疗深低温低流量缺血再灌注引发的脑白质损伤提供全新的视角。

深低温低流量(deep hypothermic low flow, DHLF)体外循环是先天性心脏病手术的重要辅助手段之一。先心病患儿正处于出生后脑白质发育的活跃期，对长时程DHLF缺血再灌注较为敏感，易引发脑白质损伤相关神经系统疾病。我们的预实验结果表明，RNA剪切调节蛋白Iws1受Akt3（蛋白激酶Bγ）磷酸化调控，并参与了长时程DHLF诱发的脑白质损伤的病理进程。Akt3在脑白质发育及稳定性维持方面的重要功能已得到广泛验证，但Iws1调控脑白质中少突胶质细胞谱系发育过程的细胞和分子机制尚不明确。我们将在分子、细胞和动物三个层次，从功能获得和缺失两个方面，研究Akt3-Iws1及其下游通路是如何介导长时程DHLF诱导的脑白质少突胶质细胞谱系发育异常的，这将为治疗深低温低流量缺血再灌注引发的脑白质损伤提供全新的视角。