摘要
目的探讨头顶一颗珠(TTM)改善冈田酸(OA)诱导的阿尔茨海默病(AD)大鼠认知功能障碍及其作用机制。方法将SD大鼠随机分为DMSO组、OA模型组、TTM治疗组。治疗组用低、中、高剂量TTM水煎液分别灌胃1周、2周。水迷宫训练后,在治疗组和模型组大鼠双侧海马注射OA(0.392 mmol·L^(-1))各1.5μL,DMSO组大鼠双侧海马各注射10%DMSO 1.5μL。注射后进行水迷宫测试,取海马和灌流取材。水迷宫测试大鼠空间学习能力;Western blot检测各组海马PP2A活性及Tau蛋白磷酸化水平;尼氏染色观察海马CA1、CA3区尼氏小体变化情况。结果水迷宫实验表明,TTM六组大鼠逃避潜伏期短于OA组;Western blot显示高剂量TTM能提高PP2A活性,减少Tau-PS396和PT404表达;尼氏染色结果表明,高剂量TTM增加尼氏小体数量。后二者具有剂量依赖性。结论 TTM能提高AD大鼠脑海马PP2A活性,降低Tau蛋白磷酸化水平,增加海马区尼氏小体数量,改善其空间记忆学习能力。
To assess the effects of Trillium Tschonoskii Maxim(TTM)decoction on learning and memory dysfunction in Alzheimer’s disease(AD)model rats which induced by okadaic acid(OA)and its possible mechanism.Methods The SD rats were divided into ten groups,namely,d DMSO control group,OA group,TTM high-dose(0.5 g·kg-1·d-1)group,TTM medium-dose(1 g·kg-1·d-1)group,TTM lower-dose(2 g·kg-1·d-1)group,and these groups were divided into one week and two weeks of gavage.Treatment groups were gavaged with TTM decoction twice a day.After 5 days of Morris water maze training,treatment groups and AD model groups were injected with OA(0.392 mmol·L^-1,1.5μL)in bilateral hippocampal of the rats.The DMSO groups were injected with 10%DMSO.The spatial memory retention wereas detected by water maze at 24 h after injection.After the test,we prepared sample for Western blot and Nissl’s staining.The Western blotting test was used to detect the PP2A activity and the phosphorylation of Tau protein in the hippocampus.Nissl’'s staining was used to observe the changes of the number of Nissl’s bodies in the hippocampal CA1 and CA3 regions.Results The Morris water maze test showed that after injection of OA,the latency of TTM groups wereas shorter than that of OA groups.Western blot showed that the high dose TTM could increase the activity of PP2A and decrease the level of Tau phosphorylation at PS-Tau396,,PT-Tau404.The Nissl’s staining results showed that the number of Nissl’s bodies in the hippocampal CA1 and CA3 regions of OA groups wereas significantly attenuated compared with that of the number of Nissl's bodies in the hippocampal CA1 and CA3 regions than DMSO groups.The number of Nissl’s bodies in high groups were morewas larger than that of OA group.Conclusion The results show that TTM can improve the learning and memory dysfunction in AD model rats which induced by OA.The mechanism wasis probably that TTM can increase PP2A activity and then down-regulate the level of Tau phosphorylation and improve neural development.
作者
谢文执
罗洪斌
谢枫枫
杨晨宇
XIE Wen-zhi;LUO Hong-bin;XIE Feng-feng;YANG Chen-yu(Dept of Biochemistry and Molecular Biology,Medical College,Hubei University for Nationalities,Hubei University for Nationalities,Enshi Hubei 445000,China;Dept of Biochemistry and Molecular Biology,Medical Faculty,Science and Technology College of Hubei University for Nationalities,Hubei University for Nationalities,Enshi Hubei 445000,China;Key Lab of Biologic Resources Protection and Utilization of Hubei Province,Hubei University for Nationalities,Enshi Hubei 445000,China;Institute of Neurological and Psychiatric Comorbidity, Hubei University for Nationalities,Enshi Hubei 445000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2018年第9期1268-1275,共8页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81260172
81660223)
湖北省自然科学基金面上项目(No 2017CFB451)
湖北民族学院科技创新团队项目(No MY2011T005)
湖北民族学院博士基金启动项目(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)
关键词
阿尔茨海默病
头顶一颗珠
PP2A
TAU磷酸化
水迷宫
尼氏染色
Alzheimer’s disease
Trillium tschonoskii Maxim
PP2A
Tau phosphorylation
water maze test
Nissl’s staining
