Wnt信号传导通路在阿尔茨海默病防治中的作用  

Role of Wnt signal transduction pathway in prevention and treatment of Alzheimer's disease

作　　者：霍江涛[1] 张小乔[1] 严洁[1] 潘庆敏[1] 陈敏[1] 

机构地区：[1]湖北医药学院附属医院老年病房,湖北十堰442000

出　　处：《中国临床研究》2015年第6期709-711,716,共4页Chinese Journal of Clinical Research

基　　金：湖北省十堰市科学技术研究与开发项目(14K68)

摘　　要：目的探讨Wnt信号传导通路在阿尔茨海默病(AD)防治中的作用,为临床治疗提供参考。方法选取C57BL/6雄性小鼠80只,均为4个月龄,随机均分为正常对照组、假手术组、模型组和丹皮酚组,每组20只。正常对照组小鼠不进行处理;模型组、丹皮酚组的小鼠均通过骨窗向脑海马部位缓慢地注入纤维型Aβ1-42溶液10μg/5μl,丹皮酚组再用丹皮酚注射液腹腔注射0.14 mg·kg-1·d-1,持续21 d;假手术组仅按照同法注入等量的生理盐水进行假手术。21 d后,观察对比小鼠脑组织P53蛋白和Caspase-3的表达(免疫组化法)情况。同时比较各组剩余小鼠3个月、6个月、1年的生存情况。结果模型组和丹皮酚组P53蛋白和Caspase-3表达明显高于正常对照组和假手术组,差异有统计学意义(P均<0.05);丹皮酚组P53和Caspase-3表达低于模型组,差异有统计学意义(P均<0.05)。对照组和假手术组小鼠的存活率明显高于模型组和丹皮酚组,差异有统计学意义(P均<0.05);丹皮酚组3个月、6个月和1年的存活率分别为70.0%、50.0%和30.0%,明显高于模型组小鼠的存活率(40.0%、10.0%和0),差异有统计学意义(P<0.05)。结论 P53和Caspase-3均参与并影响Wnt信号传导通路的转导,由于Aβ大量积聚在神经细胞内导致Wnt信号传导通路的抑制或反常活化,阻断了细胞信号向胞内的转导,导致AD。应用相应的药物(如丹皮酚)可以有效的改善Wnt信号传导通路的异常情况,这为临床治疗AD提供了新思路。Objective To investigate the role of Wnt signal transduction pathway in prevention and treatment of Alzheimer＇s disease（ AD） in order to provide theory evidence for clinical treatment of AD. Methods Eighty male C57 BL /6mice of 4 months old were randomly divided into four groups（ n = 20 each）：control group,sham operation group,model group and paeonol group. The mice in control group were not processed,In model group and paeonol group,the fiber type A beta 1-42 solution（10 μg /5 μl） was slowly injected into the brain hippocampus region through bone window,and then the paeonol injection [0. 14 mg /（ kg / d）]was given by intraperitoneal injection for 21 days in paeonol group. An equal amount of saline was injected only in accordance with the same method in sham operation group. The expressions of P53 protein and Caspase-3（ immnohistochemical method） in cerebral cortex and hippocampus region were observed and compared after 21 days,and the survival rates at 3-,6-month and 1-year of remainder mice in different groups were compared. Results The expressions of P53 protein and Caspase-3 in model group and paeonol group were significantly higher than those in control group（ all P〈0. 05）. The expressions of P53 protein and Caspase-3 in paeonol group were significantly lower than those in model group（ all P〈0. 05）. The survival rates in control group and sham operation group were significantly higher than those in model group and paeonol group（ all P〈0. 05）. The survival rates at 3-,6-month and 1-year in paeonol group（70. 0%,50. 0%,30. 0%） were significantly higher than those in model group（40. 0%,10. 0%,0,P〈0. 05）. Conclusion P53 and Caspase-3 participate in and influence the transduction of Wnt signal transduction pathway. The accumulation of a large number of A beta can cause the inhibition or anomalous activity of Wnt signal transduction pathway and block cell signal transduction toward the inside of cells,therefore lead to AD. The application of relevant drugs such

关 键 词：WNT信号传导通路 阿尔茨海默病 P53蛋白 CASPASE-3 

分 类 号：R749.16[医药卫生—神经病学与精神病学]