摘要
目的 观察大鼠弥漫性轴索损伤(DAI)后轴索及其相应的神经元β淀粉样前体蛋白(β—APP)的表达规律,以及环孢素A(CsA)对其表达的影响,探讨CsA的神经保护作用。方法 90只健康成年雄性SD大鼠随机分为3组:正常对照组(A组)8只(其中3只制作电镜标本)、DAI组(B组)41只、CsA处理组(C组)41只。对B、C两组大鼠右侧视神经施以牵拉,C组大鼠在牵拉伤后即刻按20mg/kg腹腔注射CsA。B、C组分别在伤后、CsA处理后1,3,6,12h、1,3,7d处死,其中3h、1d各为8只大鼠(3只制作电镜标本),其余时间点各5只大鼠。光镜和电镜观察神经轴索及其相应神经元胞体的病理变化;免疫组织化学方法检测视网膜神经节细胞(RGCs)和神经轴索中β—APP的表达。结果 (1)组织病理学观察:B组大鼠右侧视神经牵拉伤后神经轴索、RGCs发生明显的病理变化,C组动物相应的病理变化明显减轻;(2)β—APP表达:①B组大鼠RGCs β—APP阳性表达呈双相变化,1,3h阳性表达强度明显低于A组,1,3,7d阳性表达强度明显高于A组;C组大鼠RGCs β—APP阳性表达规律与B组相似,但1,3,7d β—APP阳性表达明显低于B组。②B组轴索β—APP阳性表达在各个时相点明显增加,3h达到高峰;C组轴索β—APP阳性表达规律与B组相似,除1h外,其余时相点阳性表达明显低于B组,但表达强度仍明显高于A组。结论 β—APP长时间过度表达可能参与了DAI后的继发性病理变化;CsA对DAI的神经保护作用可能部分与β—APP有关。
Objective To investigate the expression pattern of β-amyloid precursor protein ( β- APP) in the axons and neurons after axonal injury in rats and the effect of Ciclosporin A ( CsA ) on β- APP expression so as to explore the neuroprotective effect of CsA. Methods Ninety adult male SD rats were divided randomly into groups : control group ( Group A with 8 rats, 3 of which were used for electron microscopic examination) , stretch-only group (Group B with 41 rats), stretch plus CsA treatment group (Group C with 41 rats). Stretch injury was induced in the right optic nerves of the rats in Groups B and C. CsA at 20 mg/L was intraperitonealy injected in Group C immediately after stretch injury. Five Animals from both Group B and Group C were killed at 1, 6, 12 hours and at days 3 and 7 after stretch-injury or injection of CsA respectively, and 8 animals ( 3 of which were sacrificed for electron microscopic examination) were killed at 3 hours and 1 day. Pathological changes of the right optic nerves and neuron peri- caryon were examined by light microscope and electron microscope. Expression of β-APP in the retinal ganglion cells (RGCs) and axons were observed by means of immunohistochemistry. Results ( 1 ) Histopathological observation showed that pathological changes of the axons and RGCs after stretch injury of the fight optic nerves were identified morphologically in Group B, and significantly ameliorated by CsA treatment in Group C. (2) A diphasic change in β-APP expression in RGCs was observed in Group B, which showed significantly decreased β-APP expression at 1 and 3 hours, and significantly increased β- APP expression at days 1, 3 and 7 compared with that in Group A. The pattern of change of β-APP expression in RGCs in Group C was similar to that in Group B, but the magnitude of β-APP expression reduced significantly at days 1, 3 and 7 compared with Group B. β-APP expression in the axons in Group B increased and reached peak at 3 hours. The pattern change of β-APP
出处
《中华创伤杂志》
CAS
CSCD
北大核心
2007年第8期614-618,共5页
Chinese Journal of Trauma
基金
重庆市卫生局资助项目(99-4004)
关键词
环孢素
淀粉样β前体蛋白
免疫组织化学
轴索损伤
Cyclosporine
Amyloid beta-protein precursor
Immunohistochemistry
Axonal injuries