大鼠脑组织中甲状腺素受体THRα1的表达与阿尔茨海默病的发病机制  

An experimental study on the expression of THRα1 in brain tissues in a rat model of Alzheimer's disease

作　　者：颉宾芳[1] 孙雯雯[1] 刘卉 王佳冰[1] 刘昕[1] 

机构地区：[1]兰州大学基础医学院病理生理学研究所,兰州730000 [2]甘肃省中医学院附属医院

出　　处：《中国神经精神疾病杂志》2012年第9期530-534,共5页Chinese Journal of Nervous and Mental Diseases

摘　　要：目的观察大鼠大脑皮层和海马区脑组织中甲状腺素受体THRα1的表达与阿尔茨海默病发生的相关性并对其机制进行初步探讨。方法SD大鼠腹腔注射D-半乳糖50 mg.(kg.d)-1,复制阿尔茨海默病动物模型,另设正常对照组,腹腔注射等量生理盐水。连续给药6周后观察动物精神状态、活动情况等;取大脑皮层和海马区组织制作病理切片,光镜下观察其形态学变化;分别用实时荧光定量PCR(FQ-PCR)法和Western-blot法检测阿尔茨海默病动物与正常大鼠脑组织中THRα1、CDK-5及p35 mRNA的差异性表达和pser404-tau蛋白的表达水平。结果与正常对照组相比,阿尔茨海默病模型组动物神情呆滞,反应迟钝,镜下见大脑皮层及海马区神经元排列紊乱,核浓染、固缩,神经元轴突染色较深呈拖尾状,形成神经元纤维缠结,尤以海马区表现更为显著。与对照组相比,模型组皮层区THRα1、CDK-51和p35 mRNA表达量增加,分别为(1.20±0.30)、(4.71±0.54)、(2.11±0.40),差异有统计学意义(P<0.05);模型组海马区三者的表达量分别为(2.53±0.65)、(18.51±2.7)、(5.96±0.49),与对照组相比亦有统计学差异(P<0.05)。模型组pser404-tau蛋白呈高表达状态,与正常对照组相比P<0.05。结论大脑皮层及海马区脑组织中THRα1 mRNA的过表达及由此而加剧的神经细胞tau蛋白磷酸化可能参与或促进了大鼠阿尔茨海默病的发生发展。Objective To study the role of thyroid receptor α1 （THRα1） in brain tissues in Alzheimer＇s disease （AD）. Methods D-galactose 50 mg.（kg, d）^-1 was administered by intraperitoneal injection into SD rats to create AD model. Control animals received intraperitoneal injection of the same amount of saline. The mental status and activities were then evaluated six weeks after treatment. Histological analysis was used to examine the morphologi- cal changes in the cerebral cortex and hippocampus. Real-time fluorescence quantitative PCR and Western-blot were used to detect the mRNA expression of THRα1, CDK-5 and p35 and protein expression of pser404-tau, respectively. Results Compared with control group, AD rats looked sluggish and were unresponsive. In the brain, particularly the hippocampus of AD rats, the neuronal arrangements were disorganized, nuclei were shrunk, and neuronal axons were deeply stained in a tail-like shape, forming neurofibrillary tangles. In AD rats, the mRNA expression levels of THRα1, CDK-5 and p35 were higher in the cortex and hippocampus. In addition, the expression level of pser404- tau protein was significantly higher in AD rats than in control rats （P 〈 0.05）. Conclusions The high level of THR α1 mRNA expression and phosphorylation of protein tau in neurons of the cortex and hippocampus may contribute to the pathological process of AD in rats.

关 键 词：甲状腺素受体α1 阿尔茨海默病Tau蛋白磷酸化细胞周期素依赖性蛋白激酶5 

分 类 号：R749.16[医药卫生—神经病学与精神病学]