中华行为医学与脑科学杂志
中華行為醫學與腦科學雜誌
중화행위의학여뇌과학잡지
CHINESE JOURNAL OF BEHAVIORAL MEDICINE AND BRAIN SCIENCE
2014年
12期
1075-1078
,共4页
慢性脑缺血%蛋白磷酸酶2%学习和记忆障碍
慢性腦缺血%蛋白燐痠酶2%學習和記憶障礙
만성뇌결혈%단백린산매2%학습화기억장애
Chronic cerebral ischemia%PP2A%Dysfunction of learning and memory
目的 探讨慢性脑缺血性认知功能障碍中蛋白磷酸酶2(Protein Phosphatase 2A,PP2A)的作用和潜在机制.方法 70只雄性清洁级Sprague Dawley (SD)大鼠,分为假手术组(sham)、慢性脑缺血组(Bilateral carotid arteries occlusion,2VO)和激活PP2A(active PP2A,aPP2A)慢性脑缺血组(2VO+aPP2A),持续4周腹腔注射1.88μmol/ml硒酸钠(15 μmol·kg-1·d-1)激活PP2A或等体积生理盐水作为对照,1个月后采用双侧结扎颈总动脉方法建立慢性脑缺血模型.利用Morris水迷宫、电生理和电镜技术,检测大鼠学习记忆能力,记录长时程电位变化,观察突触前膜突触囊泡分布.结果 Morris水迷宫测试显示在训练第4～7天2VO组大鼠较假手术组大鼠有明显长的平台学习潜伏期(P＜0.05),而2VO+aPP2A组则明显短于2VO组(P＜0.01).去掉平台测试记忆显示,2VO组大鼠到达原平台位置时间明显长于假手术组[sham 组:(14.50±1.98)s vs 2VO组:(17.30±2.11)s,P＜0.01],而2VO+aPP2A组所用时间[(15.09±1.45)s]则明显短于2VO组(P＜0.05).电生理记录显示在高频刺激后2VO组的刺激前后兴奋性场电位斜率比即长时程增强(long-term potential,LTP)明显小于假手术组[假手术组:(1.69±0.27);2VO组:(2.02±0.14)](P＜0.01),而2VO+aPP2A组(1.86±0.19)则高于2VO组(P＜0.01).电镜观察并分析后显示2VO组突触前膜突触囊泡的密度明显低于假手术组[假手术组:(4.51±0.29)个/μm2;2VO组:(2.58±0.23)个/μm2] (P＜0.01),而2VO+aPP2A组[(3.58±0.50)个/μm2]则高于2VO组(P＜0.01).结论 激活PP2A可能通过调节LTP和突触囊泡密度来预防慢性脑缺血性认知功能障碍,PP2A可能是一个潜在的慢性脑缺血性认知功能障碍的防治靶点.
目的 探討慢性腦缺血性認知功能障礙中蛋白燐痠酶2(Protein Phosphatase 2A,PP2A)的作用和潛在機製.方法 70隻雄性清潔級Sprague Dawley (SD)大鼠,分為假手術組(sham)、慢性腦缺血組(Bilateral carotid arteries occlusion,2VO)和激活PP2A(active PP2A,aPP2A)慢性腦缺血組(2VO+aPP2A),持續4週腹腔註射1.88μmol/ml硒痠鈉(15 μmol·kg-1·d-1)激活PP2A或等體積生理鹽水作為對照,1箇月後採用雙側結扎頸總動脈方法建立慢性腦缺血模型.利用Morris水迷宮、電生理和電鏡技術,檢測大鼠學習記憶能力,記錄長時程電位變化,觀察突觸前膜突觸囊泡分佈.結果 Morris水迷宮測試顯示在訓練第4～7天2VO組大鼠較假手術組大鼠有明顯長的平檯學習潛伏期(P＜0.05),而2VO+aPP2A組則明顯短于2VO組(P＜0.01).去掉平檯測試記憶顯示,2VO組大鼠到達原平檯位置時間明顯長于假手術組[sham 組:(14.50±1.98)s vs 2VO組:(17.30±2.11)s,P＜0.01],而2VO+aPP2A組所用時間[(15.09±1.45)s]則明顯短于2VO組(P＜0.05).電生理記錄顯示在高頻刺激後2VO組的刺激前後興奮性場電位斜率比即長時程增彊(long-term potential,LTP)明顯小于假手術組[假手術組:(1.69±0.27);2VO組:(2.02±0.14)](P＜0.01),而2VO+aPP2A組(1.86±0.19)則高于2VO組(P＜0.01).電鏡觀察併分析後顯示2VO組突觸前膜突觸囊泡的密度明顯低于假手術組[假手術組:(4.51±0.29)箇/μm2;2VO組:(2.58±0.23)箇/μm2] (P＜0.01),而2VO+aPP2A組[(3.58±0.50)箇/μm2]則高于2VO組(P＜0.01).結論 激活PP2A可能通過調節LTP和突觸囊泡密度來預防慢性腦缺血性認知功能障礙,PP2A可能是一箇潛在的慢性腦缺血性認知功能障礙的防治靶點.
목적 탐토만성뇌결혈성인지공능장애중단백린산매2(Protein Phosphatase 2A,PP2A)적작용화잠재궤제.방법 70지웅성청길급Sprague Dawley (SD)대서,분위가수술조(sham)、만성뇌결혈조(Bilateral carotid arteries occlusion,2VO)화격활PP2A(active PP2A,aPP2A)만성뇌결혈조(2VO+aPP2A),지속4주복강주사1.88μmol/ml서산납(15 μmol·kg-1·d-1)격활PP2A혹등체적생리염수작위대조,1개월후채용쌍측결찰경총동맥방법건립만성뇌결혈모형.이용Morris수미궁、전생리화전경기술,검측대서학습기억능력,기록장시정전위변화,관찰돌촉전막돌촉낭포분포.결과 Morris수미궁측시현시재훈련제4～7천2VO조대서교가수술조대서유명현장적평태학습잠복기(P＜0.05),이2VO+aPP2A조칙명현단우2VO조(P＜0.01).거도평태측시기억현시,2VO조대서도체원평태위치시간명현장우가수술조[sham 조:(14.50±1.98)s vs 2VO조:(17.30±2.11)s,P＜0.01],이2VO+aPP2A조소용시간[(15.09±1.45)s]칙명현단우2VO조(P＜0.05).전생리기록현시재고빈자격후2VO조적자격전후흥강성장전위사솔비즉장시정증강(long-term potential,LTP)명현소우가수술조[가수술조:(1.69±0.27);2VO조:(2.02±0.14)](P＜0.01),이2VO+aPP2A조(1.86±0.19)칙고우2VO조(P＜0.01).전경관찰병분석후현시2VO조돌촉전막돌촉낭포적밀도명현저우가수술조[가수술조:(4.51±0.29)개/μm2;2VO조:(2.58±0.23)개/μm2] (P＜0.01),이2VO+aPP2A조[(3.58±0.50)개/μm2]칙고우2VO조(P＜0.01).결론 격활PP2A가능통과조절LTP화돌촉낭포밀도래예방만성뇌결혈성인지공능장애,PP2A가능시일개잠재적만성뇌결혈성인지공능장애적방치파점.
Objective To explore the roles and related mechanisms of Protein Phosphatase 2A(PP2A) in cognitive dysfunction after the chronic cerebral ischemia.Methods 70 male Sprague Dawley rats in clean degree were divided into sham group,chronic cerebral ischemia group (Bilateral carotid arteries occlusion,2VO),and chronic cerebral ischemia group with PP2A activation group(2VO+aPP2A).The rats were injected intraperitoneally with 1.88 μmol/ml sodium selenate(15 μmol · kg-1 · d-1) or equal volume of saline for 4 weeks.After one month,the chronic cerebral ischemia models were reproduced by the occlusion of bilateral common caroid artery.Then the abilities of learning and memory were tested by Morris water maze,electrophysiological indices were recorded to analyze the LTP changes,and destribution of synaptic vesicles was observed by electron microscope.Results Morris water maze test showed that the 2VO group had significantly longer latent time than sham group in searching platform(P＜0.05),and the 2VO+aPP2A group had dramatically shorter latent time (P＜0.01) than that of 2VO group.Then removing platform to test the rats memory,the data showed that 2VO group spent markedly longer time than sham group to reach the location of the former platform (sham group:(14.50±1.98)s ; 2VO group:(17.30±2.11) s) (P＜0.01),and the 2VO+aPP2A group((15.09± 1.45) s) spent dramatically shorter latent time(P＜0.05) than that of 2VO group.The electrophysiological data showed that 2VO group had the noticeably smaller field excitable postsynaptic potential slope (fEPSP) slope ratio between pre and post of the high frequency stimulations (Long-term potential,LTP) than sham group(sham group:1.69±0.27; 2VO group:2.02±0.137) (P＜0.01),and the 2VO+aPP2A group(1.86±0.19) had strikingly higher ratio than that of 2VO group(P＜0.01).The electromicroscope observation showed that presynaptic vesicles density of 2VO was remarkably lower than that of sham group (sham group:(4.51±0.29) /μm2 ; 2VO group:(2.02±0.14) /μm2) (P＜0.01),and presynaptic vesicles density of 2VO+aPP2A group((3.58±0.50) /μm2) was noticeably higher than that of 2VO group(P＜0.01).Conclusion Activating PP2A can prevent the cognitive dysfunction after chronic cerebral ischemia through regulating LTP and synaptic vesicle density.And PP2A is probably a potential target for preventing and treating the cognitive dysfunction after chronic cerebral ischemia.
