中国药理学通报2017，Vol.33Issue(8)：1060-1067,8.DOI:10.3969/j.issn.1001-1978.2017.08.006
板桥党参对激活GSK-3β诱导的AD模型大鼠认知功能障碍的保护作用及其机制
Banqiao Codonopisis Pilosula improves cognitivedysfunction induced by high GSK-3β activity and its possible mechanism
摘要
Abstract
Aim To assess the effects of Banqiao Codonopisis Pilosula(BCP)decoction on learning and memory dysfunction in AD model rats induced by high activity GSK-3β and its possible mechanism.Methods The SD rats(4 months old,♂)were divided into five groups,namely,sham-operated group(blank group),AD model group,BCP high-dose(2.16 g·kg-1·d-1)group,BCP medium-dose(1.08 g·kg-1·d-1)group,and BCP lower-dose(0.54 g·kg-1·d-1)group.Treatment group received BCP decoction by gavage once a day for 14 days,while other groups were offered drinking water by gavage once a day for 14 days.The autonomous behavior activities of all rats were observed and recorded after gavage.In the last seven days by gavage,Morris water maze test was used to test the spatial learning and memory ability of the five groups.After five days training,treatment groups and AD model group were injected wortmannin(WT,PI3K specific inhibitor)and GF-109203X(GFX,PKC specific inhibitor)(100 μmol·L-1 of each,total volume of 10 μL)into the right lateral ventricle of the rats.The blank group was only injected 2％DMSO.The spatial memory retention was detected by water maze 24 hours after lateral ventricle injection.Then,changes in the spatial learning memory of rats were observed.The level of Tau phosphorylation in SD rat hippocampus and the expression and activity changes of related protein kinase GSK-3β were detected by Western blot and immunohistochemistry.The changes of Nissl bodies in SD rat hippocampus were observed by Nissl′s staining.Results After intragastric administration of BCP,the rat autonomous behavior activities in each group all showed a declining trend,and the differences in low-dose and middle-dose groups had statistical significance compared with blank group.The Morris water maze tests showed that the latency navigation of model group was significantly longer than that of blank group(P<0.01),while that of the BCP three doses groups was shorter than that of model group(P<0.05).Compared with the same group,the latency navigation of the three groups after gavage BCP low,middle and high dose was significant shorter than that without gavage(P<0.05).Western blot results showed that the activity of GSK-3β in AD model group was up-regulated compared with the blank group.However,BCP inhibited activity of GSK-3β.Western blot and immunohistochemistry results showed the level of Tau phosphorylation in AD model group was increased compared with the blank group in the area of CA3(P<0.05).Compared with AD model group,the level of Tau phosphorylation was decreased in treatment group.Nissl′s staining results showed that dendritic spines in AD model group was significantly attenuated compared with the blank group(P<0.05).Far more dendritic spines were observed in treatment group than in AD model group.The number of Nissl′s bodies in neuron cells of hippocampus in hippocampal CA3 was obviously larger in treatment groups than in AD model group.These effect of BCP was dose-dependent.Conclusions BCP can prevent the learning and memory dysfunction in AD model rats induced by high activity of GSK-3β.The mechanism may be related to inhibiting GSK-3β activity and then reducing the level of phosphorylation of Tau and improving neural development.关键词
阿尔兹海默病/板桥党参/GSK-3β/Tau磷酸化/学习记忆能力/水迷宫Key words
Alzheimer′s disease/Banqiao Codonopisis Pilosula (BCP)/GSK-3β/Tau phosphorylation/learning and memory ability/water maze test分类
医药卫生引用本文复制引用
罗洪斌,谌勤,魏征,刘翔宇,牟南樵,陈玮,樊莎莎,谢文执,商楠,杨晨宇,谢枫枫..板桥党参对激活GSK-3β诱导的AD模型大鼠认知功能障碍的保护作用及其机制[J].中国药理学通报,2017,33(8):1060-1067,8.基金项目
国家自然科学基金资助项目(No 81260172,81660223) （No 81260172,81660223）
湖北民族学院科技创新团队项目(No MY2011T005) （No MY2011T005）
湖北民族学院博士基金启动项目(No MY2012B015) （No MY2012B015）
生物资源保护与利用湖北省重点实验室开放基金项目(No PKLHB1318) （No PKLHB1318）
