中国药理学与毒理学杂志2011，Vol.25Issue(2)：182-187,6.DOI:10.3867/j.issn.1000-3002.2011.02.011
地塞米松和淀粉样β蛋白联合作用致大鼠学习记忆能力下降
Co-administration of dexamethasone and amyloid β-protein induces learning and memory impairment in rats
摘要
Abstract
OBJECTIVE To find out whether co-administration of dexamethasone(DEX) and amyloid β-protein(Aβ) could induce learning and memory impairment in rats, and to probe its underlying mechanism. METHODS ① In vivo test All the adrenalectomized SD rats were given sc DEX 0.2 mg· kg - 1 [ as glucocorticoids (GC) maintaining group ], and additionally sc given DEX 1 and 5 mg·kg-1, Aβ25-35 5 μg, DEX 1 + Aβ25-35 and DEX 5 + Aβ25-35 as grouping. Escape latency and swim distance were measured by Morris water maze. The histopathologic changes in hippocampus CA1 field were examined under a light microscope. ② In vitro test Hippocampal neurons were incubated with DEX 1 and 10 μmol· L-1, Aβ25-35 1 and 5 μmol · L-1, ( DEX 1 + Aβ25-35 1 ),( DEX 1 + Aβ25-35 5 ), ( DEX 10 + Aβ25-35 1 ), and ( DEX 10 + Aβ25-35 5 ) μmol·L-1, respectivly.The survival rate of of hippocampal neurons was measured by colorimetric MTT assay. The lactate dehydrogenase (LDH) release rate was measured by continuous monitoring assay. Furthermore,hippocampal neurons were incubated with DEX 10 μmol·L-1 ,Aβ25-35 5 μmol·L-1, and DEX 10 +Aβ25-35 5. The tail length was assessed using alkaline single-cell gel electrophoresis. RESULTS ① In vivo test Compared with GC maintaining group , there was no statistical significance in DEX 1 mg·kg-1 group in terms of escape latency and swim distance. In DEX 5 mg·kg-1 and Aβ25-35 group, there was a slight increase in the escape latency and swim distance, but of no significant difference. In DEX + Aβ25-35 group, escape latency and swim distance significantly increased(P ＜0.05 ). The neuropathological changes were characterized by the decreased cell number, soma shrinkage and condensation, or nuclear pyknosis in DEX + Aβ25-35 group. ② In vitro test Compared with normal control group, there was no significant difference in the survival rate and LDH release rate in DEX 1, 10 μmol·L-1 and Aβ25-35 1 μmol·L-1 groups. The LDH release rate of Aβ25-35 5 μmol· L -1 group increased significantly ( P ＜ 0.05 ). Compared with the same concentration of DEX and Aβ25-35 alone treated group, co-administration of DEX and Aβ25-35 significantly decreased the survival rate and up-regulated LDH release rate( P ＜0.05 ). Compared with normal control, DEX 10 μmol·L-1 alone did not prolong the comet tail length, but Aβ25-35 5 μmol·L-1 could prolong the comet tail length. Compared with the DEX or Aβ25_35 alone treated group, co-administration of DEX and Aβ25-35 significantly increased comet tail length [( 11.8 ± 2.3 ) μm vs (9.8 ±1.8) μm; P ＜ 0.05 ]. CONCLUSION Co-adminstration of DEX and Aβ25-35 could induce learning and memory impairment and pathological damages in CA1 field of hippocampus in SD rats,which might be related to DEX potentiating the neurotoxic action of Aβ.关键词
地塞米松/淀粉样β蛋白/海马神经元/学习和记忆分类
医药卫生引用本文复制引用
姚余有,吴庆四,姬艳丽..地塞米松和淀粉样β蛋白联合作用致大鼠学习记忆能力下降[J].中国药理学与毒理学杂志,2011,25(2):182-187,6.基金项目
安徽省高校省学术带头人科学研究资助项目(2005hbz18) （2005hbz18）
安徽省教育厅高等学校优秀青年人才基金项目(2009SQRZ050) （2009SQRZ050）
安徽医科大学博士基金(XJ200820) （XJ200820）
