目的 探讨左乙拉西坦、辛伐他汀单用或联用对癫痫持续状态（SE）模型大鼠的早期神经保护作用及其相关机制。方法 利用氯化锂-匹鲁卡品制作SE大鼠模型，将造模成功的大鼠分为4组，采用不同的处理方式（生理盐水即模型组、左乙拉西坦、辛伐他汀、左乙拉西坦+辛伐他汀），同时设空白对照组，将各组大鼠处死后取脑组织，采用免疫组化尼氏染色检测大鼠海马区神经元细胞形态及数量；Western blot检测大鼠海马区calpain-1蛋白表达。结果 免疫组化尼氏染色结果显示：与空白对照组相比，模型组大鼠海马区神经元变性，存活神经元细胞减少甚至消失，正常结构消失，表明SE后24 h，大鼠海马区神经元受到了严重损伤；与模型组比较，辛伐他汀组大鼠海马区神经元减少甚至消失，排列疏松紊乱，但差异无统计学意义，表明辛伐他汀不能改变海马神经元损伤；与模型组比较，左乙拉西坦组及左乙拉西坦+辛伐他汀组大鼠海马区神经元排列尚紧密，基本保持有序，说明左乙拉西坦单用或联用辛伐他汀均能明显减少海马神经元死亡，改变海马神经元变性，差异有统计学意义（\P<0.05），但两种处理方式之间差异无统计学意义； Western blot结果显示，与空白对照组比较，模型组大鼠海马区calpain-1蛋白表达显著增高，说明calpain-1可能参与到SE神经系统损伤的病理生理机制中；与模型组比较，辛伐他汀、左乙拉西坦、辛伐他汀+左乙拉西坦组calpain-1蛋白表达降低，差异有统计学意义（\P<0.05），表明辛伐他汀、左乙拉西坦及两种药物联用均能通过降低calpain-1蛋白表达，一定程度地抑制神经兴奋毒性损伤通路。结论 左乙拉西坦可能通过抑制calpain-1发挥早期（SE后24 h）神经保护作用，然而左乙拉西坦联用辛伐他汀并未发挥更优的作用，辛伐他汀没有早期神经保护作用。
英文摘要:
Objective To determine neuroprotective properties of levetiracetam and simvastatin using rats with pilocaroine-induced epilepsy. Methods Epileptic rat models were randomly divided into 4 groups, each being exposed to saline, simvastatin, levetiracetam, or levetiracetam+simvastatin. Brain tissues of the rats were examined. Nissl staining was used to determine pilocarpine-induced neuronal loss in CA1 and CA3 of hippocampus. Western blot was used to detect calpain-1 expression of hippocampus. Results Severe cell death was found 24 h after seizures, with a level significantly higher than the controls. Compared with the saline-treated cells, simvastatin did not decrease severe cell death (\P>0.05), but levetiracetam and levetiracetam+simvastatin decreased severe cell death 24 h after seizures (\P<0.05). No significant differences were found between those treated with levetiracetam and those with levetiracetam+simvastatin. Compared with controls, overexpressed calpain-1 was found in the rats 24 h after seizures, which indicates that calpain-1 may be involved in the pathophysiological mechanisms of epilepsy. Compared with those treated with pilocarpine+saline, simvastatin, levetiracetam and levetiracetam+simvastatin reduced the level of calpain-1 24 h after seizures (\P<0.05). Conclusion Levetiracetam, not simvastatin, possesses neuroprotective properties, through changing calpain-1 expression levels. But levetiracetam plus simvastatin treatment does not have advantages over the choice of monotherapy. Simvastain does not possess neuroprotective properties at the early stage of epilepsy.
