本文選題：阿爾茲海默病 + 板橋黨參　； 參考：《中國藥理學(xué)通報》2017年08期

【摘要】：目的探索板橋黨參(BCP)水煎液對激活糖原合成酶激酶-3β(GSK-3β)誘導(dǎo)的阿爾茲海默病(AD)模型大鼠認(rèn)知功能障礙的保護作用及其可能機制。方法將50只4月齡♂SD大鼠隨機分為假手術(shù)組、AD模型組、低劑量板橋黨參組、中劑量板橋黨參組、高劑量板橋黨參組。前2組飲用水灌胃14 d,后3組灌服板橋黨參水煎液14 d。灌胃同時進行自主行為測試,d 8開始進行水迷宮訓(xùn)練。訓(xùn)練5 d后,選擇能在15 s內(nèi)找到隱藏平臺的治療組和模型組大鼠進行側(cè)腦室注射渥曼青霉素(Wortmannin,PI3K特異性抑制劑)和GF-109203X(GFX,PKC特異性抑制劑)(濃度均為100μmol·L~(-1))各5μL;假手術(shù)組注射2%DMSO 10μL。24 h后進行水迷宮測試。觀察各組大鼠側(cè)腦室注射前、后空間學(xué)習(xí)記憶力是否改變。Western blot和免疫組化檢測大鼠腦海馬組織Tau磷酸化水平及其相關(guān)蛋白激酶GSK-3β表達(dá)情況及活性變化。尼氏染色觀察神經(jīng)元尼氏小體變化情況。結(jié)果自主行為活動檢測結(jié)果發(fā)現(xiàn)板橋黨參能明顯減少大鼠活動次數(shù);水迷宮檢測結(jié)果發(fā)現(xiàn)板橋黨參能明顯改善模型大鼠認(rèn)知功能障礙;Western blot和免疫組化結(jié)果顯示模型組海馬組織GSK-3β活性升高,并導(dǎo)致Tau蛋白多個位點發(fā)生過度磷酸化,而用藥后GSK-3β活性降低,Tau蛋白多個位點磷酸化水平下調(diào);尼氏染色結(jié)果提示模型組海馬神經(jīng)元內(nèi)尼氏小體數(shù)量減少,而治療后尼氏小體增多,且呈劑量依賴性。結(jié)論板橋黨參可有效改善GSK-3β活性升高所誘導(dǎo)的大鼠認(rèn)知功能障礙,其可能機制與下調(diào)GSK-3β活性,進而抑制Tau蛋白過度磷酸化、促進神經(jīng)元發(fā)育有關(guān)。
[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.

【作者單位】： 生物資源保護與利用湖北省重點實驗室湖北民族學(xué)院醫(yī)學(xué)院生物化學(xué)與分子生物學(xué)教研室湖北民族學(xué)院神經(jīng)精神共患病研究所;
【基金】：國家自然科學(xué)基金資助項目(No 81260172,81660223) 湖北民族學(xué)院科技創(chuàng)新團隊項目(No MY2011T005);湖北民族學(xué)院博士基金啟動項目(No MY2012B015) 生物資源保護與利用湖北省重點實驗室開放基金項目(No PKLHB1318)
【分類號】：R285.5;R-332

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