A novel role of phospholipase A2 in mediating spinal cord secondary injury
A novel role of phospholipase A2 in mediating spinal cord secondary injury
复制标题
DOI：
10.1002/ana.20798
复制
发表时间：
2006-04-01
影响因子：
11.2
通讯作者：
Xu, XM
中科院分区：
文献类型：
--
作者：
Liu, NK;Zhang, YP;Xu, XM
目的：探讨磷脂酶A2（PLA 2）在脊髓损伤（SCI）发病机制中的作用。研究方法：通过生物化学、蛋白质印迹、组织学、免疫组织化学、电子显微镜、电生理学和行为学评估，研究（1）SCI诱导的PLA（2）挫伤性SCI后的活性、表达和细胞定位;（2）外源性PLA（2）对体外脊髓神经元死亡和体内组织损伤、炎症和功能的影响。结果如下：脊髓损伤后，PLA（2）活性和胞浆PLA（2）表达均显著增加，胞浆PLA（2）表达主要定位于神经元和少突胶质细胞。PLA（2）和蜂毒肽（一种内源性PLA（2）的激活剂）在体外均能诱导脊髓神经元死亡，而PLA（2）抑制剂米帕林（mepacrine）能显著逆转这种作用。将PLA（2）或蜂毒肽微量注射到正常脊髓内，前者引起局限性脱髓鞘，后者引起弥漫性组织坏死。两种注射均诱导炎症、氧化和组织损伤，导致相应的电生理和行为障碍。重要的是，PLA（2）诱导的脱髓鞘被米帕林显著逆转。Hater LA在脊髓损伤后显著增加，可能在介导脊髓损伤后神经元死亡和少突胶质细胞脱髓鞘中起重要作用。阻断PLA（2）的作用可能代表了一种新的修复策略，以减少SCI后的组织损伤和增加功能。
Objective: To investigate whether phospholipase A(2) (PLA(2)) plays a role in the pathogenesis of spinal cord injury (SCI). Methods: Biochemical, Western blot, histological, immunohistochemical, electron microscopic, electrophysiological, and behavior assessments were performed to investigate (1) SCI-induced PLA(2) activity, expression, and cellular localization after a contusive SCI; and (2) the effects of exogenous PLA(2) on spinal cord neuronal death in vitro and tissue damage, inflammation, and function in vivo. Results: After SCI, both PLA(2) activity and cytosolic PLA(2) expression increased significantly, with cytosolic PLA2 expression being localized mainly in neurons and oligodendrocytes. Both PLA(2) and melittin, an activator of endogenous PLA(2), induced spinal neuronal death in vitro, which was substantially reversed by mepacrine, a PLA(2) inhibitor. When PLA(2) or melittin was microinjected into the normal spinal cord, the former induced confined demyelination and latter diffuse tissue necrosis. Both injections induced inflammation, oxidation, and tissue damage, resulting in corresponding electrophysiological and behavioral impairments. Importantly, the PLA(2)-induced demyelination was significantly reversed by mepacrine. hater LA increased significantly after SCI, may play a key role in mediating neuronal death and oligodendrocyte demyelination following SCI. Blocking PLA(2) action may represent a novel repair strategy to reduce tissue damage and increase function after SCI.