短暂性脑缺血再灌注损伤对老年大鼠海马脑组织水通道蛋白4表达及神经元凋亡的影响  

Effects of transient cerebral ischemia and reperfusion injury on expression of aquaporin-4 and apoptosis in hippocampal neurons of aged animals： experiment with rats

作　　者：王明山 张丽娜 冀翔宇[2] 王世端[2] 万效梅 

机构地区：[1]青岛市立(东部)医院麻醉科,266071 [2]青岛大学医学院附属医院麻醉科

出　　处：《中华医学杂志》2008年第35期2504-2507,共4页National Medical Journal of China

基　　金：山东省卫生厅基金资助项目（2001CAICKAF）

摘　　要：目的探讨短暂性脑缺血再灌注损伤对老年大鼠海马脑组织水通道蛋白4表达及神经元凋亡的影响。方法健康老年Wistar大鼠160只按Pusinelli方法建立四动脉阻断法全脑缺血模型，随机分为脑缺血1min组、脑缺血3min组、脑缺血5min组和假手术组，每组40只。每组又按再灌注时间分为再灌注12h、1d、2d．3d和7d5个亚组，每个亚组8只。应用干湿重法计算脑含水量、组织病理学染色观察神经元微观结构，免疫组化方法观察AQP4的表达，TUNEL法检测神经元凋亡。结果缺血1min及3min组各再灌注时间点脑组织含水量及AQP4表达与假手术组比较差异无统计学意义（P〉0．05），而缺血5min组各再灌注时间点脑组织含水量及AQP4表达与假手术组比较差异有统计学意义（P〈0．05）。假手术组及缺血1min组有少量神经元凋亡，缺血3min及缺血5min后海马区神经元凋亡明显增加。神经元凋亡在缺血后再灌注12h即有表达，在1d达高峰，持续至第3天开始下降。结论老年脑对缺血再灌注损伤的敏感性增加，短暂的脑缺血即可造成老年大鼠脑组织的水肿和AQP4表达及神经元凋亡的增加，神经元的凋亡较脑水肿或AQP4表达对缺血更为敏感；再灌注后神经元凋亡高峰出现得早，持续时间长。Objective To investigate the effects of transient cerebral ischemia and reperfusion injury on brain edema and apoptosis hippocampal neurons of aged animals. Methods 120 19 - 21-monthold healthy Wistar rats underwent four-vossel occlusion to establish whole cerebral iscbemia model and were randomly divided into 3 equal groups to undergo ischemia for 1 min, 3 rain, and 5 wan respectively. Every group was re-divided into 5 equal sub-groups to undergo reperfusion for 12 h, 1 d, 2 d, 3 d, and 7 d respectively. Another 40 rats underwent sham operation to be used as controls. At different reperfusion time points 4 rats from each subgroup were killed to measure the wet and dry weights of the hippocampus. The brains of the remaining 4 rats from each subgroup underwent HE staining and microscopy. The expression of aquaperin-4 （AQP4） was detected by SABC immunohistochemical technique, and the neuron apeptosis in hippocampus was detected by TUNEL method. Results There was no significant differences in brain water content and expression of AQP4 between the ischemia 1 rain and 3 rain subgroups and the corresponding sham-operation subgroups（ all P 〉0. 05）, however, the brain water contents and AQP4 expression levels of the ischemia 5 min subgroups were all significantly higher than those of the corresponding sham-operation subgroups（ all P 〈0. 05 ）. There were only a few TUNEL-positive cells in the sham-operation subgroups and ischemia 1 min subgroups, however, the numbers of TUNEL-positive cells of the ischemia 3 min and 5 rain subgroups were all significantly higher. The number of TUNEL-positive cells raised 12 h after ischemia, peaked 1 day after, and began to go clown 3 clays later. Conclusion The aged animals are more sensitive to cerebral isehemia/reperfusion injury, and transient cerebral ischemia may cause brain edema, and increase of apoptotic ceils and AQP4 expression. Neuron apoptosis is more sensitive to cerebral iscbemia than brain edema and AQP4 expression. After reperfusion neuron apoptosis peaks

关 键 词：脑缺血 再灌注损伤 海马 脑水肿 水通道蛋白 凋亡 大鼠 老年 

分 类 号：R686[医药卫生—骨科学]