石杉碱甲对血管性痴呆小鼠模型海马神经细胞静息态[Ca^(2+)]i的影响  

The resting[Ca^(2+)]i level in hippocampal neurons of the mouse models with vascular dementia and the influence of Huperzine A

作　　者：吕佩源[1] 王伟斌[1] 尹昱[1] 粱翠萍[1] 李文斌[2] 

机构地区：[1]河北省人民医院神经内科,河北石家庄050051 [2]河北医科大学基础医学研究所病理生理学研究室,河北石家庄050017

出　　处：《中风与神经疾病杂志》2003年第5期409-411,共3页Journal of Apoplexy and Nervous Diseases

基　　金：河北省自然科学基金资助项目 (3 0 14 15 )

摘　　要：目的　观察血管性痴呆 (VD)小鼠海马神经细胞内静息态游离 Ca2 +浓度 ([Ca2 + ]i)变化 ,以及石杉碱甲 (哈伯因 )对 VD的治疗效果和 [Ca2 + ]i的影响 ,进而探讨 [Ca2 + ]i的改变在 VD发病机制中的作用。方法　采用双侧颈总动脉线结、反复缺血 -再灌注法 ,制作小鼠血管性痴呆动物模型 ,并设假手术组作为对照 ,服用石杉碱甲者为治疗组。分别于术后第 2 9天、第 30天进行学习、记忆和行为学测试 ;然后快速制取海马活细胞 ,以 Fluo- 3/ AM为荧光探针 ,在激光扫描共聚焦显微镜下观察各组海马神经细胞静息态 [Ca2 + ]i变化。结果　 (1)模型组的学习和记忆成绩低于假手术组及治疗组 (P<0 .0 5 ) ,治疗组及假手术组间无显著性差别 ;(2 )模型组神经细胞静息态 [Ca2 + ]i显著高于假手术组、治疗组 (P<0 .0 5 ) ,治疗组及假手术组间无显著性差别。结论　石杉碱甲作为中枢神经系统特异性胆碱酯酶抑制剂和 NMDA受体拮抗剂 ,可降低血管性痴呆小鼠海马静息态 [Ca2 + ]i,并改善其临床症状 ;因此提示 :海马神经细胞静息态 [Ca2 + ]i过高参与了血管性痴呆的发病过程。Objective To investigate the resting[Ca 2+ ]i level in hippocampal neurons of the mice with vascular dementia(VD) and the effects of Huperzine A on VD and[Ca 2+ ]i and furthermore,to explore its molecular mechanisms. Methods The mice were subjected for ischemia-reperfusion repeatly on bilateral common carotid arteries by knots to establish the VD models. Those animals with the shamed-operation were taken as control group. The treating group were administrated with Huperzine A after the establishment of VD model. The changes of behavior were observed through the step-down avoidance test and water maze test on the day 29 and 30 respectively after the operation. The hippocampal neurons were obtained immediately after mice were sacrificed and the resting[Ca 2+ ]i was measured using laser scanning confocal microscopy(LSCM) with Fluo-3/AM as fluorescence indicator. Results (1)The abilities of learning and memorizing in model group were inferior to those of shamed-operation group( P < 0.05 ) and treating group( P < 0.05 ),while there were no significant differences between control and treating groups. (2)The resting[Ca 2+ ]i levels in model group were significantly higher than those in the shamed-operation group( P < 0.05 ) and treating group( P < 0.05 ),but no significant differences were observed between control and treating groups. Conclusion Huperzine A can decrease the resting[Ca 2+ ]i,and meanwhile,improve the clinical symptoms of VD. Our study suggestes that the increased resting[Ca 2+ ]i level in hippocampal neurons participate in the pathogenesis of VD.

关 键 词：石杉碱甲 血管性痴呆 小鼠 动物模型 海马神经细胞 静息态钙离子 

分 类 号：R749.13[医药卫生—神经病学与精神病学] R-33[医药卫生—临床医学]