胰岛素生长因子-1对痴呆大鼠模型的学习记忆能力及海马超微结构的影响

目的：探讨胰岛素样生长因子-1（IGF-1）对痴呆大鼠模型学习记忆能力及海马超微结构的影响。方法：Wistar雄性成年大鼠分为正常对照组、假手术组、痴呆组、小剂量IGF-1组和大剂量IGF-1组。采用切断大鼠双侧穹窿-海马伞,建立隔-海马胆碱能系统损害的痴呆模型。痴呆模型制备1 d后开始侧脑室给药,小剂量IGF-1组给予IGF-1 10μL（0.2μg.μL-1）,大剂量IGF-1组给予IGF-1 10μL（0.5μg.μL-1）,均连续21 d;痴呆组和假手术组则在相同时间给予生理盐水10μL;正常对照组不予任何处置。利用水迷宫观察大鼠行为学改变,并用电镜观察海马神经元超微结构的改变。结果：①痴呆组与正常对照组和假手术组比较,逃避潜伏期明显延长,跨越平台次数明显减少,均差异有显著统计学意义（P〈0.01）;②小剂量IGF-1组和大剂量IGF-1组与痴呆组比较,逃避潜伏期明显缩短,跨越平台次数明显增多（P〈0.01）;③IGF-1小剂量组与大剂量组比较,逃避潜伏期明显缩短,跨越平台次数明显增多（分别P〈0.01、P〈0.05）。透射电镜观察：痴呆组海马CA1区大部分神经元肿胀、空化;神经毡呈空化改变;突触前、后膜融合,突触小泡减少。小剂量IGF-1组和大剂量IGF-1组海马CA1区均可见神经元核基质呈轻度空化改变,胞质内都可见粗面内质网、线粒体及脂褐素;神经毡内轴突内神经丝较痴呆组增多;突触小泡较多。结论：①穹隆-海马伞切断术后可导致大鼠的学习记忆能力下降;②穹隆海马伞切断术后引起大鼠海马胆碱能神经元损伤;③IGF-1可以改善痴呆模型大鼠超微结构,提高学习记忆能力。

Effects of Insulin Like Growth Factor-1 on the Abilities of Learning and Memory and Ultrastructural Changes in Hippocampus of Dementia Rats

Aim： To study the effects of insulin like growth factor-1（IGF-1） on the abilities of learning and memory and ultrastructural changes in hippocampus of dementia rats.Methods： Dementia rat models were established by transecting bilateral fornix-fimbria.Wistar male adult rats were divided into five groups： normal control group,sham group,dementia group,low dose IGF-1 group and large dose IGF-1 group.The dementia model rats received IGF-1（low dose IGF-1 group,large dose IGF-1 group） or saline（sham group,dementia group） by infused into the cerebroventricular space for 21 days after the operation.The normal control group accepted no treatment.The learning and memory abilities were measured by Morris water maze,and ultrastructural changes in hippocampus were observed under transmission electron microscopy.Results： Compared with the normal control group and the sham group,the dementia group showed the escape latency increased and the spanning platform times decreased,in which there were significant statistical differences（P0.01）.Compared with the low dose IGF-1 group and the large dose IGF-1 group,the dementia group showed the escape latency decreased and the spanning platform times increased（P0.01）.Compared with the large dose IGF-1 group,the low dose IGF-1 group showed the escape latency decreased and the spanning platform times increased（P0.01 or P0.05）.Electron microscope of dementia group showed that most of neurons were intumesce and cavitative.Neuropil was cavitated too.Pro-and post-membrane were coalesce.Synaptic vesicles decreased.Electron microscope of the low dose IGF-1 group and the large dose IGF-1 group showed nuclear matrix cavitative lightly.Rough endoplasmic reticulum,chondriosome and lipofuscin could be observed in intracytoplasm.Some nerve plexus dissolved in axis cylinder.Conclusion： Transecting hippocampal fimbria-fornix can induce the damage of neuron in hippocampal and frontal lobe,and result in the learning and memory ability of rats decreased.IGF-1 can ameliorate the learning and memory abilities of the rats.