碘乙酰胺及胰岛素对AD模型大鼠作用的初步研究  

A PRILIMINARY STUDY ON THE EFFECT OF IODOACETAMIDE AND INSULIN IN THE RAT MODEL OF ALZHEIMER'S DISEASE

作　　者：赵倩华[1] 洪震[1] 罗玉敏[1] 周玢[1] 

机构地区：[1]复旦大学附属华山医院神经病学研究所,上海200040

出　　处：《老年医学与保健》2005年第4期215-218,225,共5页Geriatrics & Health Care

摘　　要：目的探讨胰岛素降解酶激动剂碘乙酰胺及胰岛素对AD模型大鼠认知、病理及生化指标的影响。方法采用立体定向双侧海马CA3区注射Aβ42的方法建立Aβ损伤AD模型。观察碘乙酰胺、胰岛素在AD模型大鼠中的作用。实验大鼠随机分为6组:Aβ组、Aβ+碘乙酰胺组、Aβ+胰岛素组、碘乙酰胺组、胰岛素组和对照组,每组8只。各组分别接受Aβ42海马注射和碘乙酰胺皮下注射。各组大鼠于立体定向术后28d测评认知水平后处死,进行Aβ免疫组化、免疫荧光染色以及海马AβELISA定量。结果1、与Aβ组相比,Aβ+碘乙酰胺组海马Aβ沉积明显减少(23.9%),Aβ含量亦减少(24%)。此外,该组大鼠的水迷宫测试表现也优于Aβ组,具有较低的逃避潜伏期和较高的穿越平台次数。2、Aβ+胰岛素组与Aβ组比较,前者具有较多的海马Aβ沉积(增加35.7%),Aβ含量也增加(23.6%)。胰岛素干预还使大鼠的水迷宫测试表现下降:逃避潜伏期明显延长,穿越平台次数显著下降。结论1、碘乙酰胺可显著减少AD模型大鼠的Aβ沉积和认知损害程度;2、胰岛素可明显加重AD模型大鼠的Aβ沉积及认知损害。Objective To evaluate the effect of insulin and iodoacetamide on the cognition, pathology and biochemistrv in an AD rat model. Metheds 48 male Wistar rats were divided into 6 groups： A β group, A β ＋ insulin group, A β ＋ iodoacetamide group, insulin group, iodoacetamide group and the control. Each group included 8 subjects. A β was injected into the CA3 area of bilateral hippocampus. Iodoacetamide was administered subcutaneously daily lor 5 consecutive days betore surgery. And insulin was injected subcutaneously daily for 7 consecutive days pre-surgery. The behavior pertormance in the morris water maze was obtained and the level of A β was detected by immunohistochemistry staining and ELISA assay. Results A β ＋ insulin group had a much higher A β level （increased by 23.6%） and more severe A β deposit （increased by 35.7%）. Also a poorer performance in water maze was observed. Level of A β was significantly reduced in ＋ iodoacetamide group compared with that of A β group （dropped by 24%）. And tbe A β deposit decreased （by 23.9%）. The cognition function of this group also greatly improved. Conclusions Insulin can aggravate A β deposit in the hippocampus in the AD rat model and has a negative influence on its memory function. Iodoacetamide can significantly reduce the A β deposit in the hippocampus in the AD rat model and further more relieve their memory loss.

关 键 词：阿尔茨海默病 淀粉样Β蛋白 碘乙酰胺 胰岛素 疾病模型 动物 胰岛素酶 大鼠 

分 类 号：R749.1[医药卫生—神经病学与精神病学]