摘要
目的观察吗啡依赖大鼠神经元再生水平的改变及胍丁胺对抗吗啡依赖的可能机理。方法连续递增给药方式建立吗啡依赖大鼠动物模型,应用免疫组化方法检测神经元再生;应用放射免疫结合方法测定大鼠海马中cAMP水平;Westernblot方法观察大鼠海马中脑源性神经营养因子(brain derived neurotrophic factor,BDNF)和酪氨酸蛋白激酶基因TrkB水平的变化。结果连续递增给药12d造成吗啡依赖模型,吗啡抑制大鼠神经元前体细胞的增殖,胍丁胺(10mgkg-1)抑制吗啡依赖的同时可以逆转吗啡对BrdU标记的阳性细胞数目的减少,吗啡依赖大鼠BrdU阳性细胞数目下降(28±3)%;吗啡依赖大鼠海马cAMP含量下降,BDNF、TrkB水平呈现明显的下调,胍丁胺可逆转该变化。结论成年大鼠吗啡慢性处理导致依赖后,神经元再生的水平下降,胍丁胺可以减轻吗啡依赖对神经元再生的抑制作用,而吗啡对神经元再生的抑制作用与cAMP以及其介导的BDNF水平的变化密切相关。
Aim To study the effect of agmatine on the neurogenesis of adult morphine-dependent rats. Methods Repeated escalating doses of morphine injectionm were employed to induce morphine dependence. The hippocampal neurogenesis was examined by BrdU immunohistochemistry method with hippocampal frozen sections. RIA was used to determine concentration of cAMP in hippocampus and Western blotting was used to assay the change of BDNF,TrkB. Results Morphine inhibits neurogenesis of adult morphine-dependent rats and agrnatine can reverse it. In morphine-dependent rats, the expression of cAMP, BDNF, TrkB is down-regulated and agrnatine could deteriorate the change. Conclusion The influence of morphine and agrnatine on neurogenesis may be related to its modulation of cAMP and the decrease of BDNF and TrkB on hippocampus induced by cAMP.
出处
《解放军药学学报》
CAS
2006年第1期14-18,共5页
Pharmaceutical Journal of Chinese People's Liberation Army
基金
国家重点研究发展规划(973)资助项目
No.2003CB515400
国家863项目资助课题
No.2002AA2Z3028
国家自然科学基金资助课题
No.30300419
