摘要
目的:研究脑缺血及缺血后适应(postconditioning,PC)条件下,树鼩脑缺血时局部脑血流(regional cerebral blood flow,r CBF)、脑水肿及紧密连接(tight junction,TJ)的occludin和zonula occludins(ZO)-1蛋白表达的改变;探讨TJ表达对脑水肿及脑梗死的影响及其可能机制。方法:将72只健康成年树鼩随机分为对照组、脑缺血组和脑缺血+PC组,其余3只动物用于磁共振成像(MRI)观察。通过光化学反应诱导树鼩局部血栓形成;缺血PC组于缺血后4 h夹闭患侧颈总动脉3次(每次5 min)实施PC处理。用电镜观察神经超微结构,用TUNEL法检测海马神经元的凋亡数量,用激光多普勒血流监测仪检测缺血区的r CBF,用免疫组化及Western blot法观察缺血海马occludin/ZO-1蛋白的表达,MRI技术监测脑梗死体积,组织干湿法检测脑含水量的改变。结果:树鼩脑缺血后海马CA1区的正常神经元明显减少以及神经元超微结构明显异常。脑缺血组TUNEL阳性细胞数明显增加(P<0.01),r CBF明显降低,occludin/ZO-1表达减弱(P<0.01),脑含水量和脑梗死体积明显增加(P<0.01)。经PC处理的动物,缺血区r CBF增加,TJ表达增强,脑含水量降低,且TUNEL阳性细胞数和脑梗死体积明显减小(P<0.01)。结论:缺血PC可增加树鼩缺血区r CBF但不增加局部含水量;提示缺血PC缩小脑梗死体积可能与occludin/ZO-1表达增强而抑制脑水肿有关。
AIM：To assess whether the expression of tight junction（ TJ） proteins,occludin/zonula occludins（ ZO）-1,and regional cerebral blood flow（ r CBF） link to brain edema in tree shrews during thrombotic cerebral ischemia and ischemic postconditioning（ PC）,and to explore how TJ affects brain edema and cerebral infarction.METHODS：Tree shrews were randomly grouped into control,ischemia and cerebral ischemia ＋ PC（ n = 23）,and the remaining 3 animals were used for magnetic resonance imaging（ MRI）.The local cerebral thrombosis were induced by photochemical reaction in the tree shrews,and ischemic PC was established at 4 h after induction of cerebral ischemia followed by clipped ipsilateral common carotid artery（ 5 min × 3）.The changes of the neural ultrastructure were observed under electron microscope.The neuronal apoptosis was analyzed by the method of TUNEL.Laser Doppler brain flowmetry was used to monitor the r CBF.The protein levels of occludin/ZO-1 were determined by immunochemistry and Western blot.The cerebral infarction volume was detected by MRI.The brain water content was measured by dry-wet weight method.RESULTS：Induction of cerebral ischemia led to a significant reduction of the normal neuron numbers in the hippocampal CA1 area,and conversely,the number of neurons with abnormal ultrastructure was increased.The TUNEL positive cells were increased significantly（ P〈0.01） in ischemia group.Moreover,the r CBF decreased significantly（ P〈0.01）,and occludin/ZO-1protein expression decreased（ P〈0.01）.The brain water content and cerebral infarction volume were significantly increased（ P〈0.01）.Ischemic PC increased the r CBF and the occludin/ZO-1 expression,but reduced the brain water content,the TUNEL positive cells,and the infarction volume（ P〈0.01）.CONCLUSION：Ischemic PC increases the r CBF but not the local water content,suggesting that reduced cerebral infarction volume after ischemia PC is associated with the attenuation of cerebral edema by the enhan
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2016年第3期477-484,共8页
Chinese Journal of Pathophysiology
基金
国家科技支撑计划(No.2014BAI0101)
国家自然科学基金面上项目(No.30971171)
关键词
光化学反应
脑缺血
脑水肿
后适应
紧密连接蛋白
磁共振成像
树鼩
Photochemistry reaction
Cerebral ischemia
Cerebral edema
Postconditioning
Tight junction protein
Magnetic resonance imaging
Tree shrews
