凋亡信号调节激酶1上调基质金属蛋白酶-9表达促进癫痫发作  

Promotion of epileptic seizure through up-regulation of matrix metalloproteinase-9 by apoptosis signal-regulating kinase 1 in lithium-pilocarpine epilepsy model

作　　者：折潇[1] 王林[1] 张世俊[1] 张蓓[1] 李亚军[1] ZHE Xiao;WANG Lin;ZHANG Shijun;ZHANG Bei;LI Yajun(Department of Neurology,the First Affiliated Hospital of Xi′an Medical University,Xi′an 710077,China)

机构地区：[1]西安医学院第一附属医院神经内科,西安710077

出　　处：《实用医学杂志》2018年第9期1411-1415,共5页The Journal of Practical Medicine

基　　金：陕西省教育厅项目(编号:2010JK811,11JK0715);西安市莲湖区科技计划项目(编号:K2011-024);西安医学院校科研基金扶植项目(编号:2009FZ5);西安医学院附属医院院级科研立项项目(编号:XYFY-09-06)

摘　　要：目的研究癫痫大鼠海马凋亡信号调节激酶1(ASK1)激活水平和基质金属蛋白酶-9(MMP-9)表达变化,探讨其在颞叶癫痫发生中的作用与机制。方法建立锂-匹罗卡品颞叶癫痫模型,利用免疫荧光和Western blot检测ASK1磷酸化水平和MMP-9蛋白表达。应用ASK1和MMP-9抑制剂,研究ASK1对MMP-9表达的调控作用,并观察ASK1和MMP-9抑制对癫痫发作的影响。结果癫痫大鼠海马组织ASK1磷酸化水平和MMP-9表达升高(P<0.05),并与癫痫发作过程呈时间相关性。抑制ASK1激活可显著降低MMP-9的表达(P<0.05)。抑制ASK1磷酸化和抑制MMP-9表达均可有效减轻癫痫发作程度(P<0.05)。结论海马ASK1磷酸化和MMP-9表达水平在颞叶癫痫模型中明显升高,并且MMP-9表达上调由ASK1激活引起。ASK1-MMP-9信号激活在颞叶癫痫的病理进程中发挥重要作用。Objective To investigate the alteration of apoptosis signal-regulating kinase 1（ASK1）phos-phorylation and matrix metalloproteinase-9（MMP-9）expression after temporal lobe epilepsy（TLE）,and to ex-plore the role and mechanism of ASK1-MMP-9 signal in TLE. Methods The lithium-pilocarpine epilepsy modelwas established. The ASK1 phosphorylation and MMP-9 expression were detected by western blot and immunofluo-rescence histochemistry. Using ASK1 inhibitors,the regulating effects of ASK1 on MMP-9 expression were deter-mined. And the role of ASK1 and MMP-9 in epileptic seizure was explored by inhibition of ASK1 and MMP-9. Results The ASK1 phosphorylation and MMP-9 expression increased in hippocampus in epilepsy model,exhibitinga temporal correlation with epileptic seizure. Inhibition of ASK1 activation reduced the expression of MMP-9. Andthe level of epileptic seizure was significantly reduced by the inhibition of ASK1 and MMP-9. Conclusions Thehippocampal ASK1 phosphorylation and MMP-9 expression distinctly increase in TLE model,and the MMP-9 ex-pression is induced by ASK1 activation. The ASK1-MMP-9 signal plays an important role in TLE.

关 键 词：锂-匹罗卡品 凋亡信号调节激酶1 基质金属蛋白酶-9 癫痫 

分 类 号：R742.1[医药卫生—神经病学与精神病学]