板桥党参对激活GSK-3β诱导的AD模型大鼠认知功能障碍的保护作用及其机制

发布时间：2018-04-26 20:48

本文选题：阿尔兹海默病 + 板桥党参　；参考：《中国药理学通报》2017年08期

【摘要】：目的探索板桥党参(BCP)水煎液对激活糖原合成酶激酶-3β(GSK-3β)诱导的阿尔兹海默病(AD)模型大鼠认知功能障碍的保护作用及其可能机制。方法将50只4月龄♂SD大鼠随机分为假手术组、AD模型组、低剂量板桥党参组、中剂量板桥党参组、高剂量板桥党参组。前2组饮用水灌胃14 d,后3组灌服板桥党参水煎液14 d。灌胃同时进行自主行为测试,d 8开始进行水迷宫训练。训练5 d后,选择能在15 s内找到隐藏平台的治疗组和模型组大鼠进行侧脑室注射渥曼青霉素(Wortmannin,PI3K特异性抑制剂)和GF-109203X(GFX,PKC特异性抑制剂)(浓度均为100μmol·L~(-1))各5μL;假手术组注射2%DMSO 10μL。24 h后进行水迷宫测试。观察各组大鼠侧脑室注射前、后空间学习记忆力是否改变。Western blot和免疫组化检测大鼠脑海马组织Tau磷酸化水平及其相关蛋白激酶GSK-3β表达情况及活性变化。尼氏染色观察神经元尼氏小体变化情况。结果自主行为活动检测结果发现板桥党参能明显减少大鼠活动次数;水迷宫检测结果发现板桥党参能明显改善模型大鼠认知功能障碍;Western blot和免疫组化结果显示模型组海马组织GSK-3β活性升高,并导致Tau蛋白多个位点发生过度磷酸化,而用药后GSK-3β活性降低,Tau蛋白多个位点磷酸化水平下调;尼氏染色结果提示模型组海马神经元内尼氏小体数量减少,而治疗后尼氏小体增多,且呈剂量依赖性。结论板桥党参可有效改善GSK-3β活性升高所诱导的大鼠认知功能障碍,其可能机制与下调GSK-3β活性,进而抑制Tau蛋白过度磷酸化、促进神经元发育有关。
[Abstract]:Objective to explore the protective effect and possible mechanism of the decoction of Radix Codonopsis (BCP) on the cognitive dysfunction of Alzheimer's disease (AD) model rats induced by glycogen synthetase kinase -3 beta (GSK-3 beta). Methods 50 4 month old SD rats were randomly divided into sham operation group, AD model group, low dose of Codonopsis pilosula group, middle dose of Codonopsis pilosula group, high dose of Radix Codonopsis and Radix Codonopsis. Dose plate bridge Codonopsis pilosula group. The first 2 groups of drinking water gavage 14 d, the latter 3 groups of Radix Codonopsis lanceolata water decoction 14 d. irrigation at the same time test autonomous behavior, d 8 started water maze training. After training 5 d, select the treatment group which can find the hidden platform within 15 s and rats in the lateral ventricle injection of walman penicillin (Wortmannin, PI3K specificity). Inhibitor) and GF-109203X (GFX, PKC specific inhibitor) (the concentration was 100 mu mol. L~ (-1)) each 5 mu; the sham operation group injected 2%DMSO 10 mu L.24 h after the water maze test. The changes in the expression and activity of the related protein kinase GSK-3 beta. Nissl staining was used to observe the changes in the Nissl corpuscle of neurons. Results the results of spontaneous activity detection found that Banqiao Codonopsis could significantly reduce the number of activities in rats; the results of water maze detection found that Radix Codonopsis could significantly improve the cognitive impairment of model rats; Western blot and exemption. The results of phytophthoria showed that the GSK-3 beta activity in the hippocampus of the model group was increased and the multiple sites of Tau protein were overphosphorylated, and the activity of GSK-3 beta was reduced and the level of phosphorylation of multiple sites of Tau protein decreased. Nissl staining showed that the number of Nissl corpuscles in the hippocampus neurons in the model group decreased, and the Nissl corpuscles increased after treatment, and the number of Nissl corpuscles in the model group was increased. Conclusion Banqiao Codonopsis pilosula can effectively improve the cognitive impairment induced by the increase of GSK-3 beta activity, and its possible mechanism is related to the down regulation of GSK-3 beta activity, the inhibition of Tau protein overphosphorylation and the promotion of neuron development.

【作者单位】：生物资源保护与利用湖北省重点实验室湖北民族学院医学院生物化学与分子生物学教研室湖北民族学院神经精神共患病研究所;
【基金】：国家自然科学基金资助项目(No 81260172,81660223) 湖北民族学院科技创新团队项目(No MY2011T005);湖北民族学院博士基金启动项目(No MY2012B015) 生物资源保护与利用湖北省重点实验室开放基金项目(No PKLHB1318)
【分类号】：R285.5;R-332

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