神经元型一氧化氮合酶在快速衰老小鼠海马中的增龄性改变  

Aging Patterns of Neuronal Nitric Oxide Synthase in Hippocampus of Senescence Accelerated Mouse

作　　者：张立红[1] 任天华[2] 方马荣[2] 姚大卫[2] 王铭维[1] 

机构地区：[1]河北医科大学第一医院神经内科,河北石家庄050031 [2]香港中文大学医学院解剖学系

出　　处：《中山大学学报（医学科学版）》2007年第3期258-262,F0002,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：河北省科技攻关计划项目(062761820)

摘　　要：【目的】通过观察快速衰老小鼠(SAM)在衰老过程中海马中nNOS的分布和表达变化,探讨NO/nNOS在中枢神经系统衰老中的作用。【方法】采用雄性快速衰老亚系8小鼠(SAMP8)及抗快速衰老亚系1小鼠(SAMR1)为研究对象,其中SAMP8为实验组,SAMR1为对照组,每组动物再分为青年组(2月龄)和老年组(10月龄)两组,每个年龄组随机分配6只动物。用免疫组织化学法标记SAM海马中nNOS神经元,观察海马CA1,CA2和CA3区nNOS神经元的形态和分布,并计数nNOS神经元的数量;用RT-PCR法检测海马中nNOSmRNA表达水平(用平均灰度值表示)。【结果】老龄SAMP8海马中阳性神经元的形态与其它组比较无明显差别,但CA1和CA2区阳性神经元密度明显减低,CA3区阳性神经元密度无明显改变。SAMP8老年组与青年组相比,海马CA1和CA2区nNOS阳性细胞的数量显著减少(73±14vs144±38,P<0.01;71±30vs126±39,P<0.05),CA3区阳性神经元数量无显著差别;SAMP8与SAMR1比较,青年组海马nNOS阳性细胞的数量无显著差别,老年组海马CA1和CA2区阳性细胞的数量显著减少(73±14vs139±24,P<0.01;71±30vs120±37,P<0.05)。SAMP8老年组海马nNOSmRNA水平明显低于青年组(0.43±0.17vs0.92±0.15,P<0.01),且低于相应月龄SAMR1(0.43±0.17vs0.86±0.13,P<0.01)。【结论】海马中nNOS催化产生不足量NO可能加速SAMP8衰老,致使学习记忆能力下降,为通过调节NO产量来延缓衰老及衰老相关学习记忆能力下降提供了理论依据。[Objective] To observe the changes of neuronal nitric oxide synthase （nNOS） distribution and expression in the hippocampus of the senescence accelerated mouse （SAM） in the aging process and to investigate the role of nNOS in the aging central nervous system of SAM. [Method] SAM/prone8 （SAMP8） and SAM/resistantl （SAMR1） were selected as the subjects with SAMP8 as experimental group and SAMR1 as control group. Both groups were divided into young （2 months） and aged （10 months） groups. Immunohistochemical methods were used to stain nNOS positive neurons in the hippocampus of SAM. The distribution, morphology, and number of nNOS positive neurons in CAI, CA2, and CA3 regions of the hippocampus were detected. The nNOS mRNA expression levels in the hippocampus were measured by RT-PCR analysis. [ Results ] There was no significant difference in the morphology of nNOS positive neurons in the hippocampus of aged SAMP8 compared to other groups. However, the density of nNOS positive neurons decreased in CA1 and CA2 regions but no significant alterations were seen in the CA3 regions of the hippocampus. The number of nNOS positive neurons decreased in CA 1 and CA2 regions of the hippocampus （73±14 vs 144±38, P〈 0.01; 71±30 vs 126±39, P〈 0.05） but there was no significant difference in CA3 regions of aged SAMP8 compared to young SAMP8. Compared with age matched SAMR1, aged SAMP8 had significantly decreased nNOS positive neurons in CA1 and CA2 regions of hippocampus （73±14 vs 139±24, P〈 0.01; 71±30 vs 120±37, P〈 0.05） and young SAMP8 had no significant alterations of the number of nNOS positive neurons in the hippocampus. The expression of nNOS mRNA levels in the hippocampus of aged SAMP8 was significantly lower than that of young SAMP8 （0.43±0.17 vs 0.92±0.15, P〈 0.01） and also significantly lower than that of age-matched controls （0.43±0.17 vs 0.86±0.13, P〈 0.01）. [Conclusion] The downregulations of nNOS expression possibly resulted in inadequate production of NO

关 键 词：神经元型一氧化氮合酶 一氧化氮 衰老 快速衰老小鼠 海马 

分 类 号：R32[医药卫生—人体解剖和组织胚胎学]