GSK-3β/β-catenin信号通路对大鼠脑出血后神经炎症反应的调控作用  

Effects of the GSK-3β/β-catenin signaling pathway on neuroinflammatory in intracerebral hemorrhage rats

作　　者：刘爱军[1] 崔建忠[1] 王树伟[1] 卢永刚[1] 王凯杰[1] 张晓飞 洪军[1] Liu Aijun;Cui Jianzhong;Wang Shuwei;Lu Yonggang;Wang Kaijie;Zhang Xiaofei;Hong Jun(Department of Neurosurgery,Tangshan Workers Hospital,Tangshan 063000,China)

机构地区：[1]唐山市工人医院神经外科,唐山063000

出　　处：《神经解剖学杂志》2020年第6期672-678,共7页Chinese Journal of Neuroanatomy

基　　金：河北省引进留学人员资助项目(2013-140)。

摘　　要：目的:研究糖原合成酶激酶-3β(GSK-3β)/β-连环蛋白(β-catenin)信号通路在脑出血大鼠出血灶周围组织中的表达水平,并探讨其对神经炎症反应的调控作用。方法:将60只雄性SD大鼠随机分为3组:假手术组(sham)、脑出血模型组(ICH)和GSK-3β抑制剂组(SB216763)应用自体血右侧基底节区注入法建立大鼠脑出血模型,GSK-3β抑制剂组于手术前通过侧脑室注入抑制剂SB216763,用干湿重法检测脑组织含水量,ELISA法检测大鼠脑脊液中炎症细胞因子TNF-α、IL-1β及IL-6的含量,realtimeRT-PCR法检测脑出血大鼠出血灶周围组织中GSK-3β的mRNA表达水平,Western Blot检测GSK-3β、p-GSK-3β(tyr216)和β-catenin的蛋白水平。结果:与假手术组大鼠相比,脑出血组大鼠脑组织含水量增加,脑脊液中TNF-α、IL-1β及IL6的含量明显增加,出血灶周围组织中GSK-3βmRNA和蛋白表达增加,p-GSK-3β(tyr216)的水平明显升高,β-catenin蛋白表达显著下降。与脑出血模型组相比,SB216763处理组大鼠脑组织含水量增加,脑脊液中TNF-α、IL-1β及IL-6的含量明显下调,p-GSK-3β(tyr216)的水平明显降低,β-catenin蛋白表达显著上调。结论:在脑出血大鼠模型中,抑制GSK3β的活性可以显著降低大鼠脑出血后的脑水肿和神经炎症反应,其机制可能与调控Wnt/β-catenin信号通路有关。Objective: To investigate the expression of glycogen synthase kinase-3β( GSK-3β)/β-catenin signaling in perihemorrhagic brain tissues after the intracerebral hemorrhage( ICH),and its regulatory effects on neuroinflammation in rats. Methods: Sixty male SD rats were randomly divided into three groups: sham group,ICH group,and GSK-3β inhibitor SB216763 treatment group. The rat ICH model was established via intracerebroventricular infusion of autologous blood into the right basal ganglia. The rats of SB216763 group were injected into the lateral ventricle with SB216763 before operation. The brain water content was measured to evaluate brain edema in rats. The content of TNF-α,IL-1β,and IL-6 in the cerebrospinal fluid( CSF) was detected by ELISA. The mRNA expression of GSK-3β in brain parenchyma surrounding hemorrhage was detected by real time RT-PCR. The levels of GSK-3β,p-GSK-3β( tyr216),and β-catenin were determined by Western Blot. Results: Compared with sham operation group,the cerebral tissue water content of ICH group rats increased significantly;the level of TNF-α,IL-1β,and IL-6 in the CSF increased;the expression of GSK-3 mRNA and protein in the tissue surrounding the site of hemorrhage increased;the level of p-GSK-3( Tyr216) significantly increased,and the expression of β-catenin protein significantly decreased. Compared with ICH group,the cerebral tissue water content of SB216763 treatment group rats decreased significantly;the content of TNF-α,IL-1β,and IL-6 in the CSF increased;the level of p-GSK-3( Tyr216) in the tissue surrounding the site of hemorrhage decreased,and the expression of-catenin increasedp. Conclusion: GSK-3β inhibitor SB216763 treatment could confer neuroprotective effects against brain edema and neuroinflammatory response following ICH in rats,which was associated with the regulation of Wnt/β-catenin signaling pathway.

关 键 词：脑出血 糖原合成酶激酶-3Β Β-连环蛋白 神经炎症 大鼠 

分 类 号：R743.34[医药卫生—神经病学与精神病学]