脑动脉微栓子对APP／PS1双转基因小鼠脑星形胶质细胞活化和神经元凋亡的影响  

Effects of cerebral arterial microemboli on neuronal apoptosis and activation of astrocytes in APP/PS1 double tran- sgenicmice

作　　者：宁敏[1] 吴亦影[1] 倪秀石[1] 

机构地区：[1]上海交通大学附属第一人民医院老年科,上海市200080

出　　处：《老年医学与保健》2012年第5期300-304,共5页Geriatrics & Health Care

摘　　要：目的建立APP／PS1双转基因叠加脑梗死阈值下脑动脉微栓子的小鼠模型，进一步探讨脑梗死阈值下脑动脉微栓子对阿尔茨海默病的神经损伤叠加机制。方法将实验动物分为野生型小鼠对照组（n=12），APP／PS1双转基因小鼠假手术组（n=12）和APP／PS1双转基因小鼠叠加微栓子组（n=12），微栓子组经左侧颈内动脉注入25-50μm大小的全血凝块微栓子100个／300μL，假手术组和对照组注入等量的生理盐水，造模后3d和7d，HE染色观察有无梗死灶，TUNEL染色检测神经细胞的凋亡，GFAP免疫组化检测星形胶质细胞的激活。结果3组小鼠HE染色均未发现缺血梗死灶，脑梗死阈值下微栓子模型造模成功。凋亡细胞阳性率和GFAP表达阳性细胞数，对照组〈假手术组〈微栓子组，3组两两比较有统计学意义（P〈0．001）；并且在微栓子组，凋亡细胞和GFAP阳性表达随着时间的延长而增加，7d组较3d表达更多，差异有统计学意义（P〈0．001）。结论脑梗死闯值下的微栓子，虽未导致脑梗死，但可以促进APP／PS1双转基因小鼠脑胶质细胞的激活，诱发并加重AD的炎症反应进程，促进神经细胞凋亡。Objective To establish a brain injury model in APP/PS1 double transgenic mice induced by cerebral arterial microemboli in order to explore the superimposition mechanism of neuronal injury of cerebral microemboli on Alzheimer disease. Methods APP/PS1 double transgenic mice were randomly assigned to microembolic group （n = 12） and sham- operation group （n = 12）, and wild type mice were assigned to control group （n = 12）. 300 μL normal saline with 100 microemboli from whole blood clots in size of 25-50 μn were injected via left internal carotid artery in microembolic group, while 300 μL normal saline without microemboli were injected in sham-operation group and control group. Cerebral infar- ction, neuronal apoptosis and activation of astrocytes were observed with HE staining, TUNEL staining and immunohis- tochemistry staining of GFAP separately at 3 days and 7 days after surgery. Results There was no ischemic infarction in three groups, but neuronal apoptosis and activation of astrocytes showed a significam difference among three groups： control group 〈 sham-operation group 〈 microembolic group （P〈 0.001）. Furthermore, apoptotic neurons and activated astrocytes in microembolic group were more at 7 days than at 3 days （P〈0.001）. Conclusion Cerebral arterial microemboli in size under the threshold for infarction may aggravate brain activation of astrocytes and neuronal apoptosis of APP/PS1 double transgenic mice.

关 键 词：微栓子 APP/PS1双转基因 阿尔茨海默病 小鼠模型 神经元凋亡 星形胶质细胞活化 

分 类 号：R749[医药卫生—神经病学与精神病学]