神经调节素对脑缺血再灌注损伤后神经组织形态结构的影响  

The effect of neureglin on the morphology and structure of brain tissues after cerebral ischemia reperfusion injury in rats

作　　者：谷宁[1,2] 季亚清[2] 张睿[1] 郝翠[2] 李红云[1] 郭云良[2] 

机构地区：[1]青岛大学附属医院神经科,山东青岛266003 [2]青岛大学附属医院脑血管病研究所

出　　处：《中华全科医学》2016年第9期1453-1456,共4页Chinese Journal of General Practice

基　　金：山东省科技攻关计划资助项目(2010GWZ20205)

摘　　要：目的探讨神经调节素1β(NRG1β)对脑缺血再灌注损伤后改善受损神经组织形态结构的保护作用。方法应用线栓法建立大鼠大脑中动脉闭塞模型,按照随机对照原则分为假手术组、模型组、治疗组、抑制剂组、抑制剂+治疗组。经颈内动脉注射5μl(2μg/kg)NRG1β和ERK5抑制剂BIX02189 5μl(4 mg/kg)干预治疗。激光多普勒测量局部脑血流量(r CBF);TTC染色检测脑梗死体积;HE染色观察脑组织病理改变;透射电镜观察血脑屏障超微结构,免疫组化检测p ERK5表达水平。结果脑缺血后,大鼠r CBF显著下降至造模前的30%及以下,再灌注后r CBF恢复至造模前的80%及以上。模型组大鼠皮质区出现梗死灶,神经元结构损伤较重,p ERK5表达增强。与模型组比较,治疗组大鼠p ERK5表达进一步增强(P<0.05),脑梗死体积明显缩小(P<0.01),神经元结构损伤减轻。抑制剂组p ERK5表达显著降低,脑梗死体积显著增大,神经细胞损伤严重。抑制剂+治疗组大鼠p ERK5表达较抑制剂组增强(P<0.01),脑梗死体积较抑制剂组显著缩小(P<0.001),神经细胞损伤程度较抑制剂组显著减轻(P<0.001)。结论 NRG1β可能通过激活ERK5信号通路,改善梗死区脑组织的形态结构和超微结构,减轻脑组织损伤,发挥神经保护的作用。Objective To study the effect of neuregulin 1β（NRG1β） on the morphology and structure of brain tissues af- ter cerebral ischemia and reperfusion injury in rats. Methods A focal cerebral ischemic model was established by inser- ting a monofilament thread to achieve middle cerebral artery occlusion （ MCAO）, and the rats were randomly divided into 5 groups ： the sham operation group, the model group, the treatment group, the inhibitor group, the inhibitor plus treatment group. The intervention treatment was performed by internal carotid artery injection of 5 μl （2 μg/kg） NRG113. The re- gional cerebral blood flow（rCBF） was measured by Laser Doppler flowmeter （LDF）. The cerebral infarct volumes were determined by triphenyl tetrazolium chloride（TT＇C） staining. The morphology of cortical brain tissues was observed by he- matoxylin-eosin staining. The expression of pERK5 was evaluated by immunohistochemical assay. The ultrastructure of blood-brain barrier was detected by transmission electron microscope. Results After cerebral ischemia, the rCBF of rats significantly dropped to no more than 30% of the baseline, while after the reperfusion, the rCBF returned to more than 80% of the baseline. In model group, the damage of cortex infarctions, nerve cells and neurons structure was aggravating, and the expression of pERK5 protein compensatorily enhanced after cerebral ischemia reperfusion injury. Compared with the model group, the expression of pERK5 protein further enhanced（P 〈 0.05 ）, the damage of nerve cells alleviated, cere- bral infarction volume shrank （P 〈 0.01 ） in the treatment group. In the inhibitor group, cortex nerve cell seriously dam- aged, the expression of pERK.5 protein significantly decreased, the cerebral infarction volume significantly increased, and the cortex nerve cell was seriously damaged. Compared with the inhibitor group, the expression of pERK5 protein in the in- hibitor plus treatment group obviously increased （P 〈 0.01 ）, the nerve cell serious

关 键 词：神经调节素1β 脑缺血 再灌注 ERK5 超微结构 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R338.2[医药卫生—临床医学]