中华临床医师杂志（电子版）
中華臨床醫師雜誌（電子版）
중화림상의사잡지（전자판）
CHINESE JOURNAL OF CLINICIANS(ELECTRONIC VERSION)
2013年
5期
2028-2032
,共5页
脑缺血%tau蛋白质类%糖原合成酶激酶3%蛋白质磷酸酶2%氯化锂
腦缺血%tau蛋白質類%糖原閤成酶激酶3%蛋白質燐痠酶2%氯化鋰
뇌결혈%tau단백질류%당원합성매격매3%단백질린산매2%록화리
Brain ischemia%tau proteins%Glycogen synthase kinase 3%Protein phosphatase 2%Lithium chloride
目的研究大鼠慢性脑缺血过程中tau蛋白的磷酸化以及糖原合酶激酶-3β（ GSK-3β）和蛋白磷酸酶2A（ PP2A）的活性的变化。方法构建了大鼠三动脉结扎慢性脑缺血模型，通过免疫印迹的手段观察tau蛋白的磷酸化、GSK-3β和PP2A的活性，利用Morris水迷宫实验检测动物的学习与记忆能力，用组织学手段观察了大鼠海马神经元存活状况，同时研究了GSK-3β的抑制剂氯化锂对上述指标的影响。结果慢性脑缺血过程中，tau蛋白发生超磷酸化，GSK-3β的活性稍微降低，PP2A的活性大幅降低，动物学习与记忆能力显著下降，存活的海马神经元的数量大量减少。氯化锂能进一步抑制慢性脑缺血过程中GSK-3β的活性，增强PP2A的活性，降低tau蛋白的磷酸化，改善动物的学习与记忆能力，使海马神经元的数量显著增加。结论慢性脑缺血导致tau蛋白发生超磷酸化，GSK-3β和PP2A可能在其中起重要作用。超磷酸化的tau蛋白是慢性脑缺血导致脑损伤的一个重要因素。
目的研究大鼠慢性腦缺血過程中tau蛋白的燐痠化以及糖原閤酶激酶-3β（ GSK-3β）和蛋白燐痠酶2A（ PP2A）的活性的變化。方法構建瞭大鼠三動脈結扎慢性腦缺血模型，通過免疫印跡的手段觀察tau蛋白的燐痠化、GSK-3β和PP2A的活性，利用Morris水迷宮實驗檢測動物的學習與記憶能力，用組織學手段觀察瞭大鼠海馬神經元存活狀況，同時研究瞭GSK-3β的抑製劑氯化鋰對上述指標的影響。結果慢性腦缺血過程中，tau蛋白髮生超燐痠化，GSK-3β的活性稍微降低，PP2A的活性大幅降低，動物學習與記憶能力顯著下降，存活的海馬神經元的數量大量減少。氯化鋰能進一步抑製慢性腦缺血過程中GSK-3β的活性，增彊PP2A的活性，降低tau蛋白的燐痠化，改善動物的學習與記憶能力，使海馬神經元的數量顯著增加。結論慢性腦缺血導緻tau蛋白髮生超燐痠化，GSK-3β和PP2A可能在其中起重要作用。超燐痠化的tau蛋白是慢性腦缺血導緻腦損傷的一箇重要因素。
목적연구대서만성뇌결혈과정중tau단백적린산화이급당원합매격매-3β（ GSK-3β）화단백린산매2A（ PP2A）적활성적변화。방법구건료대서삼동맥결찰만성뇌결혈모형，통과면역인적적수단관찰tau단백적린산화、GSK-3β화PP2A적활성，이용Morris수미궁실험검측동물적학습여기억능력，용조직학수단관찰료대서해마신경원존활상황，동시연구료GSK-3β적억제제록화리대상술지표적영향。결과만성뇌결혈과정중，tau단백발생초린산화，GSK-3β적활성초미강저，PP2A적활성대폭강저，동물학습여기억능력현저하강，존활적해마신경원적수량대량감소。록화리능진일보억제만성뇌결혈과정중GSK-3β적활성，증강PP2A적활성，강저tau단백적린산화，개선동물적학습여기억능력，사해마신경원적수량현저증가。결론만성뇌결혈도치tau단백발생초린산화，GSK-3β화PP2A가능재기중기중요작용。초린산화적tau단백시만성뇌결혈도치뇌손상적일개중요인소。
Objective To investigate the effects of chronic brain ischemia on the phosphorylation of tau protein and the activity of Glycogen synthase kinase 3β( GSK-3β) and protein phosphatase 2A ( PP2A ). Methods Chronic brain ischemia was induced by three-vessel occlusion(3VO)in Sprague-Dawley(SD)rats.By immunoblot analysis,tau phosphorylation and the activity of GSK-3βand PP2A was examined.The learning and memory ability of rats was investigated by Morris water maze test .The number of hippocampal CA 1 pyramidal cells was examined by Cresyl Violet stainning .In the meantime , lithium chloride ( inhibitor of GSK-3β) was used to investigate above phenomenons .Results During chronic brain ischemia ,tau protein was hyperphosphorylated .The activty of GSK-3βwas modestly decreased .The activity of PP2A was heavily decreased .The learning and memory ability of rats was declined and the number of hippocampal CA 1 pyramidal cells was fewer than sham control .Lithium chloride could further inhibit the activity of GSK-3β.The activity of PP2A was increased by lithium chloride ,and the phosphorylation of tau protein was decreased by lithium chloride .The learning and memory ability of rats was improved by lithium chloride .The number of hippocampal CA 1 pyramidal cells was increased after lithium chloride treatment.Conclusions Tau protein is hyperphosphorylated in chronic brain ischemia .GSK-3βand PP2A may involved in tau hyperphosphorylaion induced by chronic brain ischemia .Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in chronic brain ischemia .
