阿尔茨海默病痰浊阻窍证大鼠tau蛋白Thr181位点特异性磷酸化改变研究

发布时间：2018-03-17 08:04

本文选题：阿尔茨海默病　切入点：痰浊阻窍证　出处：《中华中医药杂志》2017年05期 　论文类型：期刊论文

【摘要】：目的:探讨tau蛋白磷酸化在阿尔茨海默病不同中医证型中的变化特征。方法:40只雄性SD大鼠随机分为假手术组、疾病模型组、肾精亏虚证组、痰浊阻窍证组。除假手术组及疾病模型组外,其余组均予长期皮下注射D-半乳糖联合双侧海马CA1区定位注射凝聚态Aβ25-35构建病证结合肾精亏虚证大鼠模型,在此基础上痰浊阻窍证组给予高脂饲料构建痰浊阻窍证模型。采用Morris水迷宫、尼氏染色、Western blot等方法,观察各组大鼠学习记忆、海马神经元凋亡及tau蛋白过度磷酸化特异性位点的改变。结果:与假手术组比较,疾病模型组、肾精亏虚证组、痰浊阻窍证组大鼠逃避潜伏期未见明显缩短,目标象限停留时间明显减少(P0.01)、穿越平台的次数也明显减少(P0.01)。与假手术组比较,疾病模型组、肾精亏虚证组、痰浊阻窍证组尼氏染色均出现不同程度的神经元凋亡(P0.05,P0.01);与疾病模型组比较,痰浊阻窍证组凋亡最明显(P0.01)。与疾病模型组、肾精亏虚证组比较,痰浊阻窍证组大鼠海马组织tau蛋白Thr181位点的磷酸化均显著增加(P0.01)。结论:tau蛋白Thr181位点的过度磷酸化可能是AD痰浊阻窍证的特征性微观病理改变。
[Abstract]:Objective: to investigate the changes of tau protein phosphorylation in different TCM syndromes of Alzheimer's disease. Methods: forty male SD rats were randomly divided into sham operation group, disease model group and kidney essence deficiency syndrome group. Except sham-operation group and disease model group, all the other groups were given long-term subcutaneous injection of D-galactose and localization injection of condensed matter A 尾 25-35 in bilateral hippocampal CA1 region to construct the rat model of disease and syndrome combined with deficiency of kidney essence. On this basis, the model of phlegm turbid obstruction of orifices was established in the phlegm turbid obstructive orifices syndrome group with high fat feed. The learning and memory of rats in each group were observed by Morris water maze and Nissl staining Western blot. Results: compared with the sham-operated group, the escape latency of rats in the disease model group, kidney essence deficiency syndrome group and phlegm turbid obstruction syndrome group was not significantly shortened. Compared with sham operation group, the disease model group, kidney essence deficiency syndrome group, disease model group, kidney essence deficiency syndrome group, disease model group, kidney essence deficiency syndrome group, disease model group, kidney essence deficiency syndrome group, disease model group, kidney essence deficiency syndrome group, disease model group, kidney essence deficiency syndrome group, Compared with the disease model group, the apoptosis of phlegm turbid obstruction syndrome group was the most obvious (P 0.01), and compared with the disease model group and kidney essence deficiency syndrome group, the apoptosis of phlegm turbid obstruction orifices syndrome group was more obvious than that of the disease model group, and compared with the disease model group and the kidney essence deficiency syndrome group. The phosphorylation of Thr181 site of tau protein in hippocampus of rats with phlegm turbid obstruction of orifices was significantly increased (P 0.01). Conclusion the excessive phosphorylation of Thr181 site of 10 tau protein may be the characteristic microscopic pathological change of AD syndrome of phlegm turbid obstruction of orifices.
【作者单位】：山东中医药大学中医学院;山西中医学院基础医学院;中国医学科学院药物研究所&神经科学中心;湖南中医药大学药学院;山西省教育厅;
【基金】：国家自然科学基金项目(No.81573853,No.81273629) 山西省回国留学人员科研项目(No.2013-134) 中国医学科学院医学与健康科技创新工程重大协同创新项目(创新团队项目)(No.2016I2M1004) 湖南省重点研发计划项目(No.2015SK2029-1)~~
【分类号】：R277.7

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