胰岛素样生长因子-1对痴呆模型大鼠学习记忆能力影响及其可能机制

The behavior effect of IGF-1 on dementia rats and the likelihood mechanism

目的探讨胰岛素样生长因子-1(IGF-1)对痴呆模型大鼠学习记忆能力的影响及其可能机制。方法本研究采用切断成年W istar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。分为正常对照组、假手术组、痴呆组、小剂量IGF-1组、大剂量IGF-1组。痴呆模型制备1d后开始侧脑室给药,连续21d。正常对照组不给予任何处置。利用水迷宫观察其行为学改变,利用原位杂交、免疫组化及图像分析测定大鼠脑内胆碱乙酰转移酶(ChAT)和突触素的表达。结果痴呆组与正常对照组相比,其学习记忆能力明显下降,脑内ChAT及突触素的表达量明显减少(P<0.001),小剂量IGF-1组、大剂量IGF-1组大鼠的学习记忆成绩优于痴呆组(P<0.01),其脑内ChAT及突触素的表达量与痴呆组相比也明显增多(P<0.001),且小剂量IGF-1组优于大剂量IGF-1组(P<0.01)。结论IGF-1能改善痴呆模型大鼠的学习记忆能力,脑内ChAT及突触素的表达量增加是其可能机制。

Objective To study the effects of insulin-like growth factor-1 （ IGF-1 ） on the learning and memory abilities of dementia rats and to reveal the likelihood mechanism. Methods We established the dementia rat models by transecting bilateral fornix-fimbria and divided them into five groups： normal control group, sham group, dementia group, low dose IGF-1 group and large dose IGF-1 group. Dementia model rats received IGF-1 （low dose IGF-1 group,large dose IGF- 1 group）or saline （sham group, dementia group）by infusion into the cerebroventricular space for 21 days after the operation. The normal control group accept no treatment. The learning and memory abilities were measured by Morris water maze. We used hybridization in situ technique and image analysis system to observe the changes of ChAT in hippocampus and frontal lobe of dementia model rats and immunohistochemistry to observe the changes of synaptophysin. Results Compared to normal control group, learning and memory abilities of dementia group were declined and the density of ChAT and synaptophysin was decreased significantly（ P 〈 0.001 ）. In comparison with dementia control group, learning and memory abilities of low dose IGF-1 group and large dose IGF-1 group were improved and the density of ChAT and synaptophysin was increased significantly and the low dose IGF-1 group is better than the large dose IGF-I group （P 〈 0.01 ）. Conclusion IGF-1 can improve the learning and memory abilities of the dementia rats. The increasing of ChAT and synaptophysin density is the possible mechanism of the behavior effect of IGF-1 on dementia rats.