摘要
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24h,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24h)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。
Objective To determine neuroprotective properties of levetiracetam and simvastatin using rats with pilocaroine-induced epilepsy.Methods Epileptic rat models were randomly divided into 4groups,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 CA3of hippocampus.Western blot was used to detect calpain-1expression 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 hafter seizures（P〈0.05）.No significant differences were found between those treated with levetiracetam and those with levetiracetam＋simvastatin.Compared with controls,overexpressed calpain-1was found in the rats24 hafter seizures,which indicates that calpain-1may 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 hafter 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.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2015年第2期201-204,共4页
Journal of Sichuan University(Medical Sciences)
