海马注射缓激肽复制阿尔茨海默病神经原纤维变性动物模型  被引量:11

Injection of bradykinin to hippocampus induces Alzheimer-like phosphorylation of tau and abnormal behavior in rat

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作  者:王全保[1] 王建枝[1] 

机构地区:[1]中科技大学同济医学院病理生理教研室

出  处:《中华神经科杂志》2002年第4期204-206,共3页Chinese Journal of Neurology

基  金:本课题受国家自然科学基金 ( 39770 176 );国家杰出青年科学基金 ( 3992 5 0 12 );国家重点基础研究规划 (资助项目 )(G19990 5 40 0 0 )

摘  要:目的 通过海马注射缓激肽复制阿尔茨海默病神经原纤维变性大鼠模型。方法 采用脑立体定位注射技术向海马注射缓激肽 (bradykinin ,BK) ,在整体水平上调钙 /钙调素依赖性蛋白激酶 Ⅱ (CaMK Ⅱ )活性 ;电跳台法测试大鼠学习与记忆状况 ;免疫组化技术检测tau蛋白质磷酸化状况。结果 注射BK模型鼠组海马区特定位点磷酸化的tau(12E8、M4和PHF 1)其显色均强于对照组 ,模型组鼠特定位点未磷酸化的tau(tau 1)显色弱于对照组 ,并导致模型组大鼠学习记忆障碍。BK模型鼠与对照鼠出现错误次数分别为 8.3± 2 .5和 6 .9± 3.1(P <0 .0 5 ) ,受电击时间为 (73 .6± 2 5 .1)s和(35 .8± 2 3.7)s(P <0 .0 1)。结论 BK可在整体水平造成骨架蛋白tau的过度磷酸化和大鼠学习与记忆功能障碍。为复制具有AD行为及病理特征的动物模型奠定了基础。Objective To reconstitute an animal model based on the imbalance of protein kinase(s) and protein phosphatase(s) seen in Alzheimer brain. Methods The injection of bradykinin (BK) into hipocampus was performed, and their behaviors were observed by electronic attack-jump experiment and phosphorylation of tau using immunohistochemical assay. Results The results of behavior studying showed that an obvious disturbance in learning and memory was seen in BK injected rats. The results obtained by immunohistochemical assay indicated that the staining for M4?12E8?PHF-1 and CaMK-Ⅱ was stronger, and for tau-1 was weaker in BK injected rats as compared with the control group. The BK injected rats showed obvious deficit in behavior [mistakes made by model and control rats during electronic attack-jump experiment:8.3±2.5 and 6.9±3.1, P<0.05, n=24; Response to electronic attack:(73.6±25.1)s and (35.8±23.7)s, P<0.01,n=24]. Conclusions To our knowledge, this is the first data shown in vivo that the activation of CaMK-Ⅱ induces both Alzheimer-like tau phosphorylation and behavior disturbance.

关 键 词:海马 缓激肽 阿尔茨海默病 神经原纤维变性 动物模型 

分 类 号:R-332[医药卫生]

 

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