弥漫性轴索损伤发病机制及其与载脂蛋白E基因多态性相关性的研究进展

Research progress in diffuse axonal injury and its association with Apolipoprotein E polymorphism

弥漫性轴索损伤（DAI）是一种常见的原发性脑损伤，其主要损伤机制是头颅旋转运动中产生的剪切样力导致脑组织交界处产生相对位移，病理改变表现为脑白质神经纤维束的变形断裂。目前，对DAI的损伤及伤后恢复机制尚未明了，也缺乏统一的诊断标准。载脂蛋白E（APOE）基因多态性与神经系统发育及损伤、修复过程有一定相关性，APOE基因包含的3种基因相互组合形成6种基因型，合成apoE2、apoE3、apoE4三种蛋白质。其中apoE4异常的空间结构使其转运脂质的能力下降，导致神经损伤后的修复能力下降。apoE在轴索损伤发生发展过程中的分子机制较为复杂，它可以结合低密度脂蛋白结合蛋白1（LRPl）、硫酸乙酰肝素糖蛋白（HSPG）等受体蛋白介导轴索修复的过程，也能通过影响Ca2＋内流、水解产生毒性碎片等过程对神经造成损伤。而纠正apoE4的异常结构有助于神经修复，apoE类似物也具有一定的神经保护作用。笔者对DAI的损伤特点、病理特征，APOE基因多态性及合成的apoE在DAI中的作用进行综述，为进一步阐明DAI的致伤机制及临床治疗提供新的思路。

Diffuse axonal injury （DAI） is a common primary brain injury. The main mechanism of DAI is the relative displacement of brain tissue junction caused by shearing force during cranial rotation. The pathological changes are the deformation and rupture of white matter nerve fiber bundles. The mechanism of injury and recovery is still unclear, and unified diagnostic criteria are also lacking. Apolipoprotein E （APOE） gene polymorphisms are associated with nervous system development, injury, and repair process. The APOE gene contains six genotypes by the combination among three genes and synthesizes three proteins including apoE2, apoE3 and apoE4. The abnormal spatial structure of apoE4 decreases its ability of transporting lipids, resulting in reduced repair ability after nerve injury. The molecular mechanism of ApoE in the development of axonal injury is complicated, apoE protein can bind to receptor proteins such as low density lipoprotein receptor related protein 1 （ LRP1 ） and heparan sulfate proteoglycan （HSPG） to mediate axonal repair, and it can also damage nerves by influencing calcium influx and producing toxic fragments through hydrolysis. Correcting the abnormal structure of apoE4 is helpful to nerve repair, and apoE analogues also have certain neuroprotective effects. This article reviews the injury characteristics, pathological characteristics, APOE gene polymorphisms, and the role of apoE synthesis in DAI, to provide new insights for elucidation of mechanism of DAI and related clinical application.