深低温停循环诱导SUMO2/3化蛋白表达：一种新的内源性脑保护作用机制

Deep hypothermic circulatory arrest (DHCA) to carry out support for brain protection in cardiac surgery patients. The traditional view is that DHCA cerebral protection with hypothermia reduces brain metabolism to reduce related, but the mechanism has not been elucidated. View DHCA cerebral protective effect produce endogenous gene and protein expression changes related. SUMO2 / 3 of protein in the brain tissues of hibernating ground squirrels foreign study found high expression of the phenomenon, the protective effect of the body from the brain tissue protein synthesis in this process is zero, inferred protein SUMO-may ischemic brain damage have certain neuroprotective effect. In this study, we propose the following hypothesis: SUMO2 / 3 with DHCA stress-induced increased expression and activation of endogenous brain protection mechanism against DHCA brain damage following new hypothesis. The project intends to use gene transfection of RNAi lentiviral vector technology, B35 cells in low-temperature the OGD model and rat the DHCA ring model at the level of cells and animals, the observed low-temperature SUMO2 / 3 of the protein induced protective effect on the brain. Strive to a new perspective to clarify DHCA induction of endogenous brain protection mechanisms provide new targets for brain protection, which provide the basis for further research brain protected countermeasures.

深低温停循环（DHCA）开展为心脏外科术中脑保护提供了支持。传统观点认为DHCA脑保护与低温降低脑组织代谢减低有关，但是机制尚未阐明。目前有观点认为DHCA脑保护作用的产生与内源性相关基因及蛋白表达的改变相关。国外研究发现冬眠地松鼠脑组织中SUMO2/3化蛋白质出现高表达现象，而在此过程中其体内对脑组织起保护作用的一些蛋白质合成为零，据此推测蛋白质SUMO化可能对缺血性脑损伤具有一定神经保护作用。本研究我们提出以下假说：DHCA应激诱导SUMO2/3表达增高，激活内源性脑保护机制对抗DHCA后脑损伤的新假说。本项目拟用基因转染、RNAi 和慢病毒载体技术，采用B35细胞低温OGD模型和大鼠DHCA环模型在细胞和动物水平研究，观察低温对SUMO2/3化蛋白诱导及对大脑保护作用。力求从新的视角阐明DHCA诱导的内源性脑保护机制，为脑保护提供全新的靶点，从而为下一步研究脑保护的对策提供依据。

复杂先天性心脏病的治疗时需要用到深低温停循环技术，中远期随访结果发现神经系统并发症的发生率高达25%，具体的机制尚不完全清楚。小泛素化修饰蛋白（small ubiquitin-like modifier，SUMO）是一种类似于泛素的修饰蛋白。SUMO修饰是对翻译后的蛋白进行修饰，避免底物蛋白被降解从而发挥底物的生物学活性。研究发现SUMO化参与了脑保护的过程并在其中发挥重要作用。本研究目的对深低温停循环时猪的脑组织海马和皮质区SUMO1和SUMO2/3表达以及谷氨酸受体-GluK2受体在SUMO2/3化过程中起的作用。结果表明深低温停循环神经凋亡时海马和皮质区SUMO2/3化增加，通过增加GluK2受体SUMO化激活下游的MLK3-JNK3信号通路引起神经元凋亡。为研究深低温停循环脑损伤提供了新的思路和切入点。