左乙拉西坦对戊四氮致癫痫大鼠海马神经元的保护作用及NLRP1、Caspase-1和ASC蛋白的影响  

Protective Effect of Levetiracetam on Hippocampal Neurons in Rats with Epilepsy Induced by Pentylenetetrazol and Its Effects on NLRP1,Caspase-1 and ASC Protein

作　　者：许雪梅 赵元琛 张宏宇 Xu Xuemei;Zhao Yuanchen;Zhang Hongyu(Department of Pharmacy,Wenzhou Hospital of Integrated Chinese and Western Medicine,Zhejiang Wenzhou 325000,China;School of Pharmacy,Wenzhou Medical University)

机构地区：[1]温州市中西医结合医院药剂科,浙江温州325000 [2]温州医科大学药学院

出　　处：《中国药师》2019年第5期835-840,共6页China Pharmacist

摘　　要：目的:探讨左乙拉西坦对戊四氮致癫痫大鼠海马神经元的保护作用及NLRP1、Caspase-1和ASC蛋白的影响。方法:SD大鼠100只,根据体质量随机分成5组:对照组、模型组、左乙拉西坦低、中、高剂量组,试验前2周大鼠腹腔注射戊四氮35mg·kg^(-1),癫痫造模成功后,左乙拉西坦各剂量组分别给予5,10,20,mg·kg^(-1)左乙拉西坦灌胃(灌胃体积1. 0ml/100g),持续给予3周,对照组和模型组给予等体积生理盐水。试验结束后,进行Racine评分,记录癫痫发作潜伏期,以及24 h癫痫发作次数。应用Morris水迷宫试验对大鼠认知功能进行评价,获取逃避潜伏期、经过原平台位置的次数、原平台象限停留时间;检测各组大鼠海马组织NLRP1、Caspase-1和ASC蛋白表达水平。结果:与对照组比较,模型组Racine评分、潜伏期、癫痫发作次数、逃避潜伏期显著升高(P <0. 05),经过原平台位置的次数、原平台象限留的时间显著降低(P <0. 05);与模型组比较,左乙拉西坦各剂量组Racine评分、癫痫发作次数、逃避潜伏期降低,潜伏期、经过原平台位置的次数、原平台象限留的时间显著升高(P <0. 05),且随着左乙拉西坦组给药剂量的增加,Racine评分、癫痫发作次数、逃避潜伏期逐渐降低,潜伏期、经过原平台位置的次数、原平台象限留的时间逐渐升高,剂量-效应关系明显(P <0. 05);与对照组比较,左乙拉西坦各剂量组NLRP1、Caspase-1、ASC蛋白表达水平升高(P <0. 05);与模型组比较,NLRP1、Caspase-1、ASC蛋白表达水平降低(P <0. 05),且随着左乙拉西坦组给药剂量的增加,NLRP1、Caspase-1、ASC蛋白表达水平逐渐降低,剂量-效应关系明显(P <0. 05)。结论:乙拉西坦能明显抑制戊四氮致大鼠癫痫发作,减轻海马区神经元损伤程度,改善癫痫大鼠学习记忆能力;其机制可能与左乙拉西坦能明显抑制四氮致癫痫大鼠海马神经元炎性体NLRP1、Caspase-1和ASC蛋白的表达有关。Objective:To investigate the protective effect of levetiracetam on hippocampal neurons in rats with epilepsy induced by pentylenetetrazol and its effects on NLRP1,Caspase-1 and ASC protein.Methods:Totally 100 SD rats were randomly divided into 5 groups according to the body weight:the control group,the model group,and levetiracetam group respectively at low,medium and high dose.Two weeks before the experiment,the rats were used to establish epileptic model by intraperitoneal injection of 35 mg·kg^-1 pentylenetetrazol.After the model establishment,the rats in levetiracetam groups were given 5,10 or 20 mg·kg^-1 levetiracetam,while the control group and the model group received the equal volume of normal saline.Thereafter,the Racine score,seizure latency and onset frequency of seizure within 24 h were recorded.Morris water maze test was used to evaluate the cognitive function of rats,and the indicators including the escape latency,frequency of crossing original platform and percentage of time staying at original platform quadrant were obtained.Meanwhile,the protein expression levels of NLRP1,Caspase-1 and ASC in hippocampus of each group were detected.Results:The Racine score,latency,seizure frequency and escape latency ranked in a descending order was the model group,levetiracetam groups and the control group,and the decrease effect in levetiracetam groups was more significant with the increase of the dosage(P<0.05).The frequency of crossing original platform and percentage of time staying at original platform quadrant ranked in an ascending order was the model group,levetiracetam groups and the control group,and the increase effect in levetiracetam groups was more significant with the increase of the dosage(P<0.05).The protein expression levels of NLRP1,Caspase-1 and ASC ranked in a descending order was the model group,levetiracetam groups and the control group(P<0.05).The above effect in levetiracetam groups had a dose-effect manner(P<0.05).Conclusion:The application of levetiracetam can significantly inhibit t

关 键 词：左乙拉西坦 戊四氮 癫痫大鼠 海马神经元 半胱氨酸蛋白酶 ASC蛋白 

分 类 号：R965.1[医药卫生—药理学]