摘要
目的:利用小鼠急性全脑缺血模型观察急性脑缺血对海马神经发生的影响。方法:将C57BL/6雄性小鼠(6~8周)随机分为脑缺血组和假手术组。采用双侧颈动脉结扎法建立短暂性全脑缺血模型;利用HE染色观察脑缺血后不同时间(1周,2周)海马区形态学变化;采用免疫组织荧光染色观察缺血后海马区caspase-3表达变化;利用Ed U染色观察缺血3 d、7 d、14 d和28 d后,海马区神经干细胞增殖变化;利用免疫组织荧光染色观察缺血3 d、7 d、14 d和28 d后,海马区nestin、胶质纤维酸性蛋白(GFAP)及少突胶质细胞特异蛋白(OSP)等蛋白表达变化,判断脑缺血对海马区神经干细胞分化的影响。结果:脑缺血7 d后,小鼠海马CA1区神经元数目减少,caspase-3阳性细胞增加(P<0.05)。海马DG区Ed U阳性细胞数量在第3 d开始增加(P<0.05),第1周达到峰值(P<0.05);海马CA1区Ed U阳性细胞数量在缺血后1周开始增加(P<0.05),缺血2周后逐渐降低。海马DG区nestin、GFAP及OSP阳性细胞数量均在缺血3 d后开始增加(P<0.05),缺血1周后达到峰值(P<0.05),2周后逐渐降低。海马CA1区GFAP及OSP阳性细胞数量在缺血3 d后开始增加(P<0.05),缺血1周后达到峰值(P<0.05),2周后逐渐降低。结论:脑缺血激活了海马DG区神经干细胞,使干细胞增殖,并向神经元、星形胶质细胞、少突胶质细胞分化,同时逐渐向CA1区迁移。
Objective： To investigate the transient cerebral effect of ischemia on hippocampal neurogenesis by an established ischemic mouse model. Methods： Twenty-five male C57 BL/6 mice（ 6-8 weeks） were randomly divided into cerebral ischemia group（ n = 20） and sham operation group（ n = 5）. The ischemic model was set up by bilateral carotid arteries occlusion. At 3 d,1 week,2 week and 4 weeks after ischemia,the hippocampal morphological change was observed by HE staining; the proteins expression of caspase-3,nestin,glial fiblillary acidic protein（ GFAP） and oligo-dendrocyte specific protein（ OSP） were examined by immunohistofluorescence staining; the activation of hippocampal neurogenesis was observed by Ed U staining. Results： The number of neurons was decreased in hippocampal CA1 region at 1 week after ischemia,also the caspase-3 positive cells number was increased at the same time. The Ed U positive cells number were increased at 3 days and peaked at 1 week in DG region after ischemia,it increased at 1 week in CA1 region.The nestin,GFAP and OSP positive cells number was increased at 3 days,peaked at 1 week and decreased at 2 weeks in DG region after ischemia. The GFAP and OSP positive cells number were increased at 3 days,peaked at 1 week and decreased at 2 week in CA1 region（ P〈0. 05）. Conclusion： Cerebral ischemia active the hippocampal DG neurogenesis and promote neural stem cells differentiate into neurons,astrocytes,oligodendrocytes.
作者
孙文青
姚子昂
金毅然
马海滨
牛建国
何仲义
梁雪云
Sun Wenqing;Yao Ziang;Jin Yiran;Ma Haibin;Niu Jianguo;He Zhongyi;Liang Xueyun(School of Clinical Medicine, Ningxia Medical University;Departmem of Histology and Embryology, School of Basic Medicine, Ningxia Medical University;Ningxia Human Stem Cell Research Institution, General Hospital of Ningxia Medical University;Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan 750004, China)
出处
《神经解剖学杂志》
CAS
CSCD
北大核心
2018年第2期175-183,共9页
Chinese Journal of Neuroanatomy
基金
国家自然科学基金(81460186)
宁夏自然科学基金(NZ14130)
关键词
脑缺血
神经干细胞
神经发生
海马
神经干细胞分化
cerebral ischemia
neural stem cell
neurogenesis
hippocampus
neural stem cell differentiation
