摘要
目的观察FKBPs(FK506 blinding proteins)配体噻嗪酰胺衍生物(HD5-6)对SAMP8快速老化小鼠学习记忆能力和海马神经元的影响,以及对SAMP8小鼠海马神经元基因表达谱的影响。方法选用10月龄快速老化的SAMP8小鼠20只,随机分为痴呆组、HD5-6组;另选10月龄正常老化的SAMR1小鼠10只作为正常对照组。各组分别腹腔注射药物35 d,并于29 d采用Morris水迷宫实验评价各组小鼠学习记忆能力的变化。HE染色观察海马区神经元形态;TUNEL观察海马神经元凋亡情况,用基因芯片技术检测HD5-6组和痴呆组小鼠海马神经元基因表达谱的变化差异。结果与正常对照组相比,痴呆组在定位航行实验中表现出明显的学习记忆障碍,逃避潜伏期显著延长(P<0.05),HD5-6组自3 d开始逃避潜伏期比痴呆组明显缩短(P<0.05);空间探索实验中HD5-6组跨平台次数、原平台象限停留时间明显多于痴呆组(P<0.05)。与正常对照组相比,痴呆组海马区神经元数量明显减少,细胞排列紊乱,大量的神经元细胞核固缩,深染、坏死,其神经元凋亡指数(51.73±4.48)%明显高于正常对照组(28.02±11.25)%(P<0.05),HD5-6干预的SAMP8小鼠海马区神经元病理改变明显改善,海马神经元凋亡指数(20.47±2.25)%明显降低(P<0.01)。HD5-6组与痴呆组海马神经元基因表达谱相比,表达差异在2倍以上的基因有118条,表达上调的为9条,表达下调的为109条。其中有功能的mRNA中,表达上调的有4条,表达下调的有21条。结论 HD5-6能够改善快速老化小鼠SAMP8的学习记忆能力和海马神经元病理改变,并可能通过对基因表达谱产生影响而发挥明显的抗衰老作用。
Objective To observe the anti-aging effect of the novel FKBPs ligand, Thiazine amides derivatives （HDS-6） , on the changing of learning and memory ability, the pathological changes and the gene expression profiles in se nescence accelerated-prone mouse 8 （SAMPS）. Methods 20 SAMP8 mice （10-month-old） were randomly divided into Dementia group and HD5-6 group,10 senescence accelerated-resistant mice （SAMR1,10-Month-old） were assigned to the normal group. Each group of mice were injected by the corresponding solution for 35 days. After administrated for 29 days, Morris water maze test was used to assess the learning and memory abilities changing of each group of mice. After 35 days, HE staining was used to observe the pathological changes of hippocampus neuron. TUNEL assay was used to observe the neuron apoptosis index. The differences of gene expression profiles between the dementia and the HDS-6 group were ana- lyzed by gene microarray technology. Results The dementia group showed significant learning and memory deficits in Spa- tial acquisition compared to the normal group with prolonged escape latency （ P 〈 0.05 ）. The escape latency was signifi cantly shortened in HD5-6 group on day3 （P 〈 0.05）. The times that mice crossing the plateau region and the time in orig inal platform quadrant in spatial probe test were significantly increased in HD 5-6 group （P 〈 0.05）. The neuron numbers in hippocampus of the dementia group decreased significantly compared with those in the normal group. The neuron apopto sis index of the dementia group was （51.73 ±4.48 ） %, that is obviously higher than that in normal group （28.02 ± 11.25 ） % （ P 〈 0.05 ）. While these pathological changes were significantly improved in the HD 5-6 group with the apopto sis index（20.47 ± 2.25 ）%. Totally 118 mRNA had more than two fold different expression, in which up-regulated and down-regulated genes were 9 and 109 respectively. There were 4 genes up-regulated and 21 genes down-regulated in func
出处
《中风与神经疾病杂志》
CAS
CSCD
北大核心
2014年第1期4-8,共5页
Journal of Apoplexy and Nervous Diseases
基金
国家自然科学基金项目(No.81100962)
