布洛芬对慢性癫痫模型大鼠的神经保护作用及其机制研究  

Neuroprotective effect of ibuprofen on chronic epilepsy and its mechanism in rats models

作　　者：刘睿 彭江涛 胡忠波[1] 郭科[1] 郭翀 张鑫帆 吴淑华[2] 李建民[1] Liu Rui;Peng Jiangtao;Hu Zhongbo;Guo Ke;Guo Chong;Zhang Xinfan;Wu Shuhua;Li Jianmin(Department of Neurosurgery,Affiliated Hospital of Binzhou Medical University,Binzhou 256600,China;Department of Pathology,Affiliated Hospital of Binzhou Medical University,Binzhou 256600,China)

机构地区：[1]滨州医学院附属医院神经外科,滨州256600 [2]滨州医学院附属医院病理科,滨州256600

出　　处：《中华神经医学杂志》2020年第9期916-923,共8页Chinese Journal of Neuromedicine

基　　金：山东省医药卫生科技发展计划(2017WS553)。

摘　　要：目的探讨布洛芬对慢性癫痫模型大鼠的神经保护作用以及对海马区NOD样受体蛋白3(NLRP3)炎性小体及其相关产物的影响。方法SD大鼠30只按随机数字表法分为对照组、癫痫组、布洛芬干预组,每组10只。癫痫组大鼠每隔1天腹腔注射戊四氮(PTZ)(35 mg/kg)1次,布洛芬干预组大鼠每隔1天在注射PTZ前30 min腹腔注射布洛芬(30 mg/kg)1次,对照组大鼠每隔1天腹腔注射等量生理盐水,共注射15次。最后一次注射后观察大鼠10 min,记录各组大鼠癫痫发作的潜伏期、癫痫发作级别、是否完全点燃;应用脑电图检测各组大鼠的脑异常放电情况;4 h后采用HE及Nissl染色检测各组大鼠海马区神经元损伤比例,采用免疫组化染色、Western blotting实验分别检测各组大鼠海马NLRP3炎性小体、半胱氨酸天冬酶-1(Caspase-1)、白介素(IL)-18阳性细胞的吸光度值和蛋白的表达。结果(1)与癫痫组比较,布洛芬干预组大鼠完全点燃发生率低,且潜伏期长,发作级别低,差异均有统计学意义(P<0.05)。癫痫组大鼠的脑电图可见棘波及高幅尖波痫样放电;布洛芬干预组大鼠的脑电图呈低幅度小棘波、棘慢波。(2)与对照组比较,癫痫组和布洛芬干预组大鼠海马区神经元损伤比例明显增高;与癫痫组比较,布洛芬干预组大鼠海马区神经元损伤比例明显降低,差异均有统计学意义(P<0.05)。(3)与对照组比较,癫痫组和布洛芬干预组大鼠海马NLRP3炎性小体、Caspase-1、IL-18阳性细胞的吸光度值和蛋白的表达均增高;与癫痫组比较,布洛芬干预组大鼠海马NLRP3炎性小体、Caspase-1、IL-18阳性细胞的吸光度值和蛋白的表达均降低,差异均有统计学意义(P<0.05)。结论布洛芬可以抑制癫痫模型大鼠海马NLRP3炎性小体、Caspase-1、IL-18的表达,降低癫痫发作强度,起到神经保护作用。Objective To investigate the neuroprotective effect of ibuprofen,and influence of ibuprofen in hippocampal nod-like receptor protein 3(NLRP3)inflammatome and its related products in chronic epilepsy rats models.Methods Thirty male SD rats were randomly divided into 3 groups:control group,pentylenetetrazol(PTZ)group and PTZ+ibuprofen group(n=10).Rats in the PTZ group were intraperitoneally injected with PTZ(35 mg/kg)once every one d,and rats in the PTZ+ibuprofen group were intraperitoneally injected with ibuprofen(30 mg/kg)once every one d 30 min before PTZ injection;rats in the control group were intraperitoneally injected with the same amount of normal saline every one d.Injection for 15 times was performed.After the last injection,the rats were observed for 10 min,and the latency,seizure level and complete ignition of the rats in each group were recorded.Electroencephalogram(EEG)was used to detect the abnormal brain discharge in rats.Four h after last injection,HE staining and Nissl staining were used to detect the proportion of damaged hippocampal neurons in each group.Immunohistochemical staining was used to detect the absorbance values of NLRP3 inflammasome,caspase-1 and interleukin(IL)-18 positive cells in the hippocampus of rats in each group;Western blotting was used to detect the protein expressions of NLRP3 inflammatome,caspase-1 and interleukin(IL)-18 in the hippocampus of each group.Results(1)As compared with the PTZ group,rats in the PTZ+ibuprofen group had statistically lower incidence of complete ignition,significantly longer latency and significantly lower seizure level(P<0.05).EEG showed spikes and high amplitude epileptic wave discharge in rats of the PTZ group;EEG showed low amplitude small spiny wave and slow spiny wave in rats of the PTZ+ibuprofen group.(2)As compared with the control group,the proportion of injured hippocampal neurons significantly increased in the PTZ group and PTZ+ibuprofen group(P<0.05);and the proportion of injured hippocampal neurons in the PTZ+ibuprofen group signfican

关 键 词：癫痫 布洛芬 NOD样受体蛋白3炎性小体 半胱氨酸天冬酶-1 白介素-18 神经保护 

分 类 号：R742.1[医药卫生—神经病学与精神病学]