全身麻醉药对大脑髓鞘发育、维持与损伤修复的影响及机制研究

全球每年有数亿患者的手术在全身麻醉药的使用下完成。已有的全身麻醉药仍有很多不足，如有报道全身麻醉药可导致术后认知功能障碍。而全身麻醉药如何造成这些损伤的机制还知之甚少。少突胶质细胞包裹轴突形成髓鞘对于神经元的功能是至关重要的，大量研究表明髓鞘与大脑认知功能等密切相关，髓鞘异常会造成学习记忆障碍。已有报道全身麻醉药可导致包含少突胶质细胞在内的多种神经细胞凋亡，但是其对髓鞘有何影响尚不清楚。我们对出生后的小鼠使用丙泊酚后检测到髓鞘蛋白的减少，提示全身麻醉药可能对髓鞘结构有影响。本项目在前期研究基础上，结合药物和转基因模型，综合利用分子，生化和细胞生物学等实验技术来研究全身麻醉药对髓鞘发育、维持及损伤修复的作用及分子机制。本项目将能揭示全身麻醉药对中枢神经系统髓鞘发育，维持及髓鞘损伤修复的调控及其分子机制，为预防和处理全身麻醉药引起的大脑功能障碍提供新的思路和靶点。

General anesthetics were used by thousands of million patients during surgery every year. The common general anesthetics had many defects. It was reported that they can cause brain dysfunction such as cognitive disorders. However, the mechanisms underlying the effects of general anesthetics on brain function are not fully understood. In the central nervous system, the oligodendrocytes(OLs)-formed myelin is critical for the neuronal function. Myelin disorder causes brain dysfunction such as Learning and memory Impairment. It was reported that general.anesthetics leaded to neural cells death included OLs. But it is unclear whether they can affect myelin in the brain or not. After propofol injection in the newborn mice, we found myelin related protein downregulation in the brain, indicating that general anesthetics may involve in myelin regulation. In this project, we will continue to utilize molecular biological, biochemical and cellular.biological approaches to study the myelin development, the myelin maintaining and remyelination under general anesthetics treatment and their underlying mechanisms. Our results will reveal the mechanisms of roles of general anesthetics in myelination, myelin maintaining and remyelination in the brain and supply new prevention and therapeutic target for brain dysfunctions related to general anesthetics treatment.