布洛芬对癫痫大鼠自噬和星形胶质细胞增生的影响及意义  

Effect of ibuprofen on autophagy and astrocyte proliferation and their significances in epileptic rats

作　　者：彭江涛 胡忠波[1] 郭翀 刘睿 吴淑华[2] 李建民[1] Peng Jiangtao;Hu Zhongbo;Guo Chong;Liu Rui;Wu Shuhua;Li Jianmin(Department of Neurosurgery,Affiliated Hospital of Binzhou Medical University,Binzhou 256600,China;Department of Pathology,Affiliated Hospital of Binzhou Medical College,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》2019年第7期678-683,共6页Chinese Journal of Neuromedicine

基　　金：山东省医药卫生科技发展计划(2017WS553);滨州医学院科技计划项目(BY2015KJ13).

摘　　要：目的探讨布洛芬对戊四氮(PTZ)点燃癫痫大鼠自噬和星形胶质细胞增生的影响。方法选用雄性SD大鼠60只,按照随机数字表法分为对照组、PTZ组、3-MA+PTZ组、布洛芬+PTZ组和3-MA+布洛芬+PTZ组,每组12只。后4组应用PTZ阻断γ-氨基丁酸活性的机制点燃癫痫大鼠,对照组每隔1天给予生理盐水腹腔注射1次。3-MA+PTZ组、布洛芬+PTZ组大鼠每次PTZ注射前30min给予3-MA(2.5mg/kg)或布洛芬(30mg/kg)腹腔注射。3-MA+布洛芬+PTZ组同样时间给予3-MA(2.5mg/kg)+布洛芬(30mg/kg)腹腔注射。观察大鼠行为学表现和脑电图情况,采用免疫荧光染色及Western blotting实验检测微管相关蛋白1轻链3(LC3)和胶质纤维酸性蛋白(GFAP)的表达情况。结果(1)与PTZ组和3-MA+PTZ组比较,布洛芬+PTZ组、3-MA+布洛芬+PTZ组癫痫发作等级、完全点燃发生率明显下降,潜伏期明显增加,差异均有统计学意义(P<0.05)。(2)与PTZ组和3-MA+PTZ组比较,布洛芬+PTZ组和3-MA+布洛芬+PTZ组脑电图波峰明显减小,呈频发低幅的小棘波和棘慢波,其中布洛芬+PTZ组变化更明显。(3)免疫荧光染色及Westernblotting实验结果均显示,与PTZ组比较,3-MA+PTZ组LC3表达降低,GFAP表达升高,差异有统计学意义(P<0.05)。与PTZ组相比,布洛芬+PTZ组LC3水平升高,GFAP水平降低,差异有统计学意义(P<0.05)。与布洛芬+PTZ组比较,3-MA+布洛芬+PTZ组LC3表达降低,GFAP表达升高,差异有统计学意义(P<0.05)。结论布洛芬可通过促进自噬减少星形胶质细胞增生进而影响癫痫发作。Objective To investigate the effect of ibuprofen on autophagy and astrocyte proliferation and their significances in rats with pentylenetetrazol(PTZ)-induced epilepsy. Methods Sixty male sprague-dawley rats were randomly divided into control group, PTZ group, 3-MA+PTZ group, ibuprofen+PTZ group and 3-MA+ibuprofen+PTZ group (n=12);activity of gamma-aminobutyric acid was blocked by PTZ to ignite epileptic rats in the latter 4 groups, and rats in the control group were intraperitoneally injected with normal saline once every one day;rats in the 3-MA+PTZ group and ibuprofen+PTZ group were given intraperitoneal injection of 3-MA (2.5 mg/kg) or ibuprofen (30 mg/kg) 30 min before PTZ injection;rats in the 3-MA+ibuprofen+PTZ group were given intraperitoneal injection of 3-MA (2.5 mg/kg)+ibuprofen (30 mg/kg) at the same time. The behavior and EEG features of rats were observed. Immunofluorescence staining and Western blotting were used to detect the expressions of microtubule-associated protein 1 light chain 3 (LC3) and glial fibrillary acidic protein (GFAP). Results (1) As compared with rats in the PTZ group and 3-MA+PTZ group, rats in the ibuprofen+PTZ group and 3-MA+ibuprofen+PTZ group had significantly decreased seizure grading and incidence of complete ignition, and significantly increased latency period (P<0.05).(2) The EEG waveform of the control group was normal;electroencephalogram of PTZ group and 3-MA+PTZ group showed sharp waves of high amplitude and spike waves;EEG wave peaks in the ibuprofen+PTZ group and 3-MA+ibuprofen+PTZ group decreased significantly, presenting frequent small spike waves and slow spike waves, among which ibuprofen+PTZ group showed more obvious changes.(3) The results of immunofluorescence staining and Western blotting showed that as compared with the PTZ group, 3-MA+PTZ group had statistically decreased LC3 expression and significantly increased GFAP expression (P<0.05);as compared with the PTZ group, ibuprofen+PTZ group had statistically increased LC3 expression and significantly decrea

关 键 词：癫痫 星形胶质细胞 自噬 布洛芬 

分 类 号：R742.1[医药卫生—神经病学与精神病学]