托吡酯对新生大鼠脑白质损伤保护作用的研究

摘要:目的　观察托吡酯对新生大鼠脑白质损伤的保护作用。方法　采用右侧颈总动脉结扎加缺氧处理的2日龄SD大鼠脑白质损伤（White Matter Damage，WMD）模型，检测WMD模型后12 h、24 h、48 h及72 h脑白质丙二醛（Malondialdehyde，MDA）和超氧化物歧化酶（Superoxide Dismutase，SOD）含量的改变，并与对照组大鼠比较。WMD模型组大鼠分别加用托吡酯30 mg/kg（托吡酯干预组）和DMSO（非干预组）腹腔注射5次后检测脑白质MDA的改变，电镜观察大鼠脑白质髓鞘化形成情况。结果　WMD各组大鼠脑白质MDA含量明显高于对照组（P＜0.001），SOD活性低于对照组（P＜0.001）；托吡酯干预组MDA水平明显低于非干预组（P＜0.001）。电镜观察显示，托吡酯干预组大鼠脑白质髓鞘化程度明显好于非干预组。结论　新生大鼠脑缺氧缺血后，脑白质SOD含量下降，MDA随着缺氧缺血时间的延长而生成增多；托吡酯对新生大鼠脑白质损伤具有保护作用。

The protective effect of topiramate on white matter damage in neonatal rats

Abstract: Objective The study was conducted to observe the protective effect of topiramate on white matter damage (WMD) in neonatal rats. Methods A WMD model was established by treating 2-day-old SD rats with right common carotid artery ligation combined with hypoxia treatment. The changes in malondialdehyde (MDA) and superoxide dismutase (SOD) levels in the brain white matter of the WMD model after 12 h, 24 h, 48 h, and 72 h were measured and compared with the control group. The WMD model rats were then intraperitoneally injected with 30 mg/kg of topiramate (intervention group) and DMSO (non-intervention group) for five times. The change in MDA in the brain white matter was measured, and myelination of the brain white matter in the rats was observed by electron microscopy. Results MDA contents in the brain white matter of rats in all WMD groups were significantly higher than that in the control group (P<0.001); SOD activities of the WMD groups were lower than that of the control group (P<0.001); and MDA level of the intervention group was significantly lower than that of the non-intervention group (P<0.001). Electron microscopic observation showed that myelination of the brain white matter in the rats in the intervention group was significantly better than that in the non-intervention group. Conclusion After occurrences of hypoxic and ischemic damage in the brain of neonatal rats, SOD level in the brain white matter would decrease and MDA would increase with the length of time of hypoxic-ischemic damages. Topiramate is shown to protect neonatal rats against hypoxic-ischemic damage in the brain white matter.