摘要目的 观察慢性脑低灌注模型大鼠海马组织胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)/IGF-1受体(IGF-1 receptor,IGF-1 R)信号通路与学习记忆功能的动态变化,探讨血管性痴呆(vascular dementia,VaD)的可能机制.方法 采用永久性双侧颈总动脉结扎法制作大鼠慢性脑低灌注模型；在模型制作后3d、1周、2周、1个月、2个月和4个月时,采用水迷宫实验检测大鼠学习记忆功能的变化；HE染色观察海马神经元形态学改变；酶联免疫吸附法检测海马组织IGF-1、IGF -1R、Akt和p-Akt的动态变化.结果 模型组大鼠在造模后1个月开始出现明显的学习记忆功能障碍,穿越平台次数显著性低于假手术组[(1.91±0.45)次对(3.95±1.64)次；t=17.251,P=0.000].随着缺血时间的延长,模型组大鼠海马CA1区锥体细胞损伤程度逐渐加重.模型组海马组织IGF-1和p-Akt含量在模型制作后早期增高,之后逐渐降低至正常水平,1个月时IGF-1[ (0.09±0.05) ng/mg对(0.20±0.03) ng/mg;t=-5.263,P=0.003]和p-Akt[(12.50±1.40)ng/mg对(17.13±0.87) ng/mg;t=-5.651,P=0.000]含量均显著低于假手术组,并持续至4个月时；IGF-1R和Akt含量无显著改变.结论 海马IGF-1/IGF-1R信号通路下调可能是VaD的发病机制之一.

abstractsObjective To investigate the dynamic changes of hippocampal insulin like growth factor-1(IGF-1)/IGF-1 receptor (1GF-1 R) signaling pathway and learning and memory function and to investigate the possible mechanisms of vascular dementia (VaD).Methods A rat chronic cerebral hypoperfusion model was induced by using permanent bilateral common carotid artery ligation.At day 3,1 and 2 weeks,1,2 and 4months after modeling,Morris water maze test was used to evaluate the changes of learning and memory function in rats.HE staining was used to observe the morphological changes of hippocampal neurons.Enzymelinked immunosorbent assay was used to detect the dynamic changes of IGF-1,IGF-1R,Akt and p-Akt in hippocampal tissue.Results One month after modeling,the rats of a model group began to appear significant learning and memory dysfunction.The numbers of crossing the platform were significant lower than those in a sham operation group (1.91 ±0.45 times vs.3.95 ± 1.64 times; t =17.251,P =0.000).With the extension of ischemia time,the degree of injury of pyramidal cells in hippocampal CA1 region aggravated gradually in the model group.The levels of IGF-1 and p-Akt in hippocampal tissue increased early after modeling in the model group,and then they declined gradually to the normal levels.The levels of IGF-1 (0.09 ± 0.05 ng/mg vs.0.20 ±0.03 ng/mg; t =-5.263,P =0.003) and p-Akt (12.50± 1.40 pg/mg vs.17.13 ± 0.87 pg/mg; t =- 5.651,P =0.000) at 1 month were significantly lower than those in the sham operation group and continued to 4 months.There were no significant changes in the levels of IGF-1R and Akt.Conclusions The down-regulation of IGF-1/IGF-1R signaling pathway may be one of the pathogeneses of VaD.