trkA和Aβ1-40与阿尔茨海默病大鼠发病机制的关系.docVIP

trkA和Aβ1-40与阿尔茨海默病大鼠发病机制的关系 【摘要】 目的 采用穹隆-海马伞切断及双侧卵巢切除的 方法 制作阿尔茨海默病（AlzhEimer,disease AD）模型，观察AD模型大鼠脑内皮层区、海马CA1区、杏仁复合体区和Meynert核区酪氨酸激酶原癌基因（tyrosine kinase proto-onco-geneA,TrkA）和β淀粉样肽1-40（Amyliod β1-40）的表达与对照组比较有何变化，以探讨二者的变化与AD发病机制的关系。方法 取健康雌性Wistar大鼠20只，随机分成四组，对照组，穹隆海马伞切断加卵巢切除组（双切加去势组），卵巢切除组（去势组），穹隆海马伞切断组（双切组）每组各5只。在脑立体定位仪上，切断大鼠脑的双侧穹隆海马伞同时切除双侧卵巢，建立模拟AD的动物模型。 应用 免疫组织细胞化学技术对trkA和Aβ1-40免疫阳性细胞染色。观察AD模型组大鼠脑皮层区、海马CA1区、杏仁复合体区和基底前脑Meynert核区等部位trkA和Aβ1-40阳性细胞的表达与对照组比较是否不同。结果 对照组大鼠脑内的各观察区内Aβ1-40只有少量表达，trkA表达无明显改变；AD模型组大鼠脑内的皮层区、海马CA1区、杏仁复合体区和基底前脑Meynert核区Aβ1-40表达显著增多（P0.05），各模型组zhijian 相互比较，Aβ1-40的表达无明显差异（P0.05）；AD模型组大鼠脑内的皮层区、海马CA1区、杏仁复合体区和基底前脑Meynert核区trkA的阳性细胞显著减少（P0.05），各模型组之间相互比较，穹隆海马伞切断加卵巢切除组较穹隆海马伞切断组和卵巢切除组trkA减少显著（P0.05），穹隆海马伞切断组与卵巢切除组之间trkA表达差异无显著性（P0.05）。结论 AD模型组大鼠脑内皮层区、海马CA1区、杏仁复合体区和基底前脑Meynert核区内Aβ1-40的阳性细胞显著增加，而trkA的阳性细胞显著减少，提示Aβ1-40的表达增多和trkA的表达减少可能与老年性痴呆发病机制相关，可能是临床AD发病的病理基础。 【关键词】 穹隆-海马伞切断；卵巢切除；酪氨酸原癌基因；β淀粉样肽1-40；大鼠；阿尔茨海默病 【Abstract】 Objective To observe the expression of trkA and Aβ1-40 in the different areas of the brain when the ovaries of rats were ablated and those bilateral fimbria/fornix were transected in order to make AD model and discuss the relationship of trkA and Aβ1-40 with the pathogenesis of AD. Methods Totally 20 health female rats were randomly and equally divided into control group, fimbria/fornix transection and ovariectomized group, ovariectomized group and fimbria/fornix transaction group. The bilateral fimbria-fornix of brain was transected in the fimbria/fornix transaction group. The bilateral ovaries of rats were ablated in the ovariectomized group. In the fimbria/fornix transection and ovariectomized group, bilateral fimbria-fornix of brain were transected and meanwhile bilateral ovaries of rats were ablated to make simulational model of AD. Immunoreactive cell of trkA and Aβ1-40were stained by immunohistochemical way. The expressive varieties of immunoreactive cell of trkA and Aβ1-40 in the cerebral cortex, hippocampus CA1, M