高血糖和脑缺血对树鼩海马继发性损伤及VEGF表达关系的影响  

Effect of relationship on the hippocampal secondary neuronal injury and VEGF expression during hyperglycemia and brain ischemia in tree shrews

作　　者：陈静[1] 李树清[1] 

机构地区：[1]昆明医科大学病理生理学教研室,云南昆明650500

出　　处：《中风与神经疾病杂志》2013年第8期676-680,共5页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金(30971171)

摘　　要：目的研究高血糖及脑缺血条件下树鼩海马继发性损伤模式与VEGF表达变化的相互关系,探讨半暗区神经元损伤与抗损伤反应变化的规律及机制。方法制备树鼩高血糖模型和光化学诱导的皮层血栓性脑缺血模型,通过TTC染色观察缺血后4h、24h、72h树鼩脑皮层梗死范围,并检测患侧海马CA1、CA3和DG区神经元密度变化,用免疫组化法观察上述时点海马不同区域VEGF表达的动态变化。结果光化学反应后,不仅在照射区皮层可见明显梗死灶,同侧海马内也存在缺血损伤性变化。正常血糖缺血组海马细胞损伤主要发生在CA1区,呈"选择性易损"的特点;高血糖缺血组皮层梗死范围更大,海马神经元密度更低,且海马CA3和DG区也受累及。免疫组化染色显示,皮层梗死后,海马结构内VEGF表达也被激活,CA1区对VEGF的表达更为敏感,于缺血后4h升高,24h达高峰,72h逐渐下降;而CA3和DG区只在损伤最重的缺血后24h点VEGF表达升高才具有统计学差异。单纯升高血糖使VEGF表达上调也"选择性"地发生在海马CA1区。结论 (1)海马继发性损伤具有选择性易损和缺血耐受的双重特点,其损伤模式的可变性受环境因素(如:高血糖)的影响。(2)脑缺血和高血糖均可激活VEGF表达,VEGF表达的时空特点与海马神经元继发性损伤的变化规律具有相对的一致性,提示VEGF表达在海马选择性易损现象中可能具有重要作用。Objective To investigate the relationship between pattern of hippocampal secondary neuronal injury and VEGF expression during hyperglycemia and brain ischemia in tree shrews,to explore the mechanisms of secondary neuronal injury and against injury reaction in the penumbra region.Methods High blood glucose and photochemical focal cortical thrombotic cerebral ischemia in tree shrews was induced.At 4h,24h and 72h after cerebral ischemia,the cortical infarct size were examined by TTC staining.The neuronal density were determined in the affected hippocampal CA1 、CA3 and DG subfields.VEGF expression in the hippocampal was detected by immunohistochemistry technology at different time points after cerebral ischemia.Results The histopathological study showed that there was ischemic damage involving in the exposured cerebral cortex and the ipsilateral hippocampal region after the photochemical reaction.The hippocampal ischemic damage occurred mainly in the CA1 sector in normoglycemic ischemic group,showing the characteristics of selective vulnerability.The animals in hyperglycemic ischemic group suffered from serious neurological lesion in the cortex and hippocampus.The ischemic lesion was also involved in hippocampal CA3 and DG sectors.Immunohistochemical analyses revealed that VEGF expression was increased significantly in the hippocampus after cortical infarction.It was more sensitive to ischemia in hippocampal CA1 sector,and it started to increase at 4h after brain ischemia,reached a peak at 24h,and weakened at 72h gradually.However,in hippocampal CA3 and DG sectors,the elevation of VEGF expression was statistically significant only at 24h after brain ischemia,when the damage was most severe.The stimulated VEGF production also only occurred in the hippocampal CA1 subfield in hyperglycemic sham group.Conclusion（1） The hippocampal secondary neuronal injury has a dual characteristics of both selective vulnerability and relative tolerance to ischemia.The variability of damage pattern can be attributed to the extrinsi

关 键 词：脑缺血 高血糖 海马 血管内皮生长因子 树鼩 

分 类 号：R743.3[医药卫生—神经病学与精神病学]