神经调节素1β对脑缺血再灌注后神经元损伤的保护机制  

Study of neuron-protective effect and mechanism of neuregulin1β against cerebral ischemia reperfusion-induced injury in rats

作　　者：季亚清[1] 张睿[1] 滕蕾[1] 李红云[1] 郭云良[1] 

机构地区：[1]青岛大学附属医院脑血管病研究所,266003

出　　处：《中华医学杂志》2017年第27期2128-2134,共7页National Medical Journal of China

基　　金：国家自然科学基金（81274116）

摘　　要：目的探讨神经调节素1β（NRG-1β）在MCAO/R后通过抑制c-Jun磷酸化从而保护神经元的机制及意义。方法采用改良Longa法制备大鼠脑缺血2 h再灌注24 h模型，改良神经功能缺损评分（mNSS）评价神经行为功能，TTC染色测量梗死体积，伊文思蓝法检测血脑屏障（BBB），尼氏染色检测神经元形态，透射电镜检测神经元的超微结构，TUNEL及NeuN双染色检测神经元凋亡，免疫荧光双标及Western印迹检测phospho-c-Jun的蛋白定位、定量及共表达。 结果与假手术组相比，大鼠MCAO/R后mNSS评分升高[（9.7±1.2）分]，梗死体积增大（41.4±3.0）%，BBB的完整性破坏，神经元形态结构异常，神经元凋亡细胞数增多（0.63±0.04），神经元phospho-c-Jun蛋白表达增强（0.90±0.07）（P〈0.05）。NRG1β处理后可改善大鼠神经行为功能[（6.4±0.9）分]，减少脑梗死体积[（10.4±0.5）%]，降低伊文思蓝渗透率（1.55±0.13），减轻神经元的异常形态结构，降低神经元凋亡细胞数（0.23±0.02），抑制神经元c-Jun的磷酸化（0.40±0.03）（P〈0.05）。结论NRG1β在对脑缺血再灌注损伤的神经保护作用机制可能与抑制c-Jun的磷酸化有关。ObjectiveThecurrent study is to explore the neuron-protective mechanism of neuregulin1β （NRG1β） in a rat model of middle cerebral artery occlusion/reperfusion （MCAO/R） through inhibiting the c-Jun phosphorylation.MethodsAfter 24 h of MCAO/R （referring to Longa′s method）, neurobehavioral function was measured by modified neurological severity score （mNSS） test; the cerebral infarction volume was detected by triphenyltetrazolium chloride （TTC） staining; the blood brain barrier （BBB） permeability was measured by Evans Blue （EB）; the neuron morphology of brain tissue was observed by Nissl stain; the ultra-structures of the neurons were observed by transmission electron microscopy （TEM）; the apoptotic neurons were counted by in situ cell death detection kit colocalized with NeuN; the expressions of phospho-c-Jun was determined by immunofluorescent labeling and Western blot analysis.ResultsCompared with the sham-operation rats, the rats receiving MCAO/R showed increased mNSS （9.7±1.2）, cerebral infarction volume （41.4±3.0）%, permeability of BBB, deformation of neurons, ischemia-induced apoptosis （0.63±0.04）, and enhanced expression of phospho-c-Jun protein （0.90±0.07） （all P〈0.05）. Our data indicated that NRG1β attenuated neurologic deficits （6.4±0.9）, decreased the cerebral infarction volume （10.4±0.5）, reduced EB extravasation （1.55±0.13） and the deformation of neurons, protected the ultra-structure of neurons, blocked ischemia-induced apoptosis （0.23±0.02）, through down-regulated phospho-c-Jun expression （0.40±0.03） in MCAO/R rats （P〈0.05）.ConclusionNRG1β exerts neuron-protective effects against ischemia reperfusion-induced injury in rats through inhibiting the c-Jun phosphorylation.

关 键 词：神经调节素1β 脑缺血再灌注 神经元 C-JUN 

分 类 号：R743[医药卫生—神经病学与精神病学]