β-淀粉样蛋白和胆固醇对大鼠大脑类似阿尔茨海默病病理学进程和尼古丁受体的影响

目的探讨β-淀粉样蛋白（Ag）和胆固醇与阿尔茨海默病（AD）病理学进程和神经型尼古丁受体的关系。方法Wistar大鼠经侧脑室注射Aβ1-42（1mg／ml,5μl／只）来建立类似AD动物模型,并饲以5％胆固醇饮食。采用银染、免疫组织化学、水迷宫、Western blot和逆转录聚合酶链反应（RT-PCR）等方法检测实验动物脑组织形态学、学习记忆能力、神经型尼古丁受体亚单位表达水平等方面的改变。结果Aβ侧脑室注射引起大鼠脑组织中AB沉积;高胆固醇饮食造成大鼠明显高胆固醇血症（血胆固醇浓度较对照组增高21％～24％）;Aβ侧脑室注射引起大鼠学习记忆力降低,导致尼古丁受体α3、α4和α7亚单位蛋白水平降低（较对照组分别降低46％、39％及51％）,并引起酊亚单位mRNA表达水平升高41％-73％;高胆固醇饮食能够明显增强Aβ引起的脑组织中Aβ沉积和星形胶质细胞增多、学习记忆能力降低及尼古丁受体表达改变。结论Aβ能明显引起大鼠大脑病理学改变,降低大鼠学习记忆能力和影响神经型尼古丁受体的表达;高胆固醇饮食可增强Aβ的神经毒性作用及对尼古丁受体的影响。

Influence of beta-amyloid protein and cholesterol on the pathological changes of Alzheimer's disease and expression of nicotinic acetylcholine receptors in rats

OBJECTIVE: To study the influence of beta-amyloid protein (Abeta) and cholesterol on the pathological changes of Alzheimer's disease (AD) and on the expression of nicotinic acetylcholine receptor (nAChR) subunits in the brains of rats. METHOD: The rats were treated by intracerebroventricular injection of Abeta1-42 and fed with a diet containing 5% cholesterol to establish animal model of AD. The pathological changes, learning and memory, and expression of nAChRs of rats were analyzed by Bieoschowsky staining, immunohistochemistry, water-labyrinth, Western blot, and RT-PCR. RESULTS: Abeta intracerebroventricular injection induced Abeta deposition in rat brains and high-cholesterol diet resulted in hypercholesterolemia in the animals. Injection of Abeta caused a reduction of learning and memory of rats and modifications of the expression of nAChRs. Cholesterol enhanced these effects of Abeta on neuropathology and expression of nAChRs. CONCLUSIONS: Abeta can induce marked neuropathological changes, influence the learning and study ability, and modify the expression of nAChRs. Cholesterol can enhance the neurotoxicity of Abeta.