本文選題：阿爾茲海默病　切入點：板橋黨參　出處：《湖北民族學院》2017年碩士論文

【摘要】：目的:本課題主要研究板橋黨參(Banqiao Codonopisis Pilosula,BCP)是否具有改善阿爾茲海默病(Alzheimer's disease,AD)模型大鼠認知功能障礙的作用,并通過檢測大鼠海馬組織Tau蛋白磷酸化水平及其相關激酶活性、神經發(fā)育等內容,探索其可能作用機制。方法:用不同劑量BCP水煎液對擬激活糖原合酶3β(Glycogen synthase 3β,GSK-3β)的AD模型大鼠進行灌胃處理。其中灌胃第9天進行Morris水迷宮訓練,灌胃第13天進行側腦室注射磷脂酰肌醇3-激酶特異性抑制劑渥曼青霉素(Wortmannin,WT)和蛋白激酶C特異性抑制劑GF-109203X(GFX),灌胃第14天進行水迷宮測試,檢測各組大鼠空間認知功能。運用免疫印跡、免疫組織化學法檢測大鼠海馬Tau磷酸化水平變化情況及其與之密切相關的蛋白激酶GSK-3β活性變化,運用尼氏染色法觀察大鼠海馬區(qū)神經元形態(tài)變化以及神經細胞功能情況。結果:1.自主行為測試結果顯示給大鼠灌服板橋黨參水煎液后,三個治療組均比未給藥組大鼠自主活動次數(shù)減少,且隨著時間推移自主活動次數(shù)逐漸減少。2.水迷宮測試表明治療組能明顯改善AD模型大鼠認知功能障礙。3.Western Blot結果顯示AD模型組總的GSK-3β無變化,但是活性T216-GSK-3β比假手術組高(p0.05),而且p-Tau231、p-Tau262、p-Tau396、p-Tau404表達增加(p0.05)。板橋黨參干預后Tau蛋白特殊位點磷酸化水平明顯下調(p0.05)。4.免疫組織化學法檢測腦海馬組織Tau蛋白磷酸化修飾情況,結果顯示:AD模型組海馬CA3區(qū)Tau蛋白磷酸化程度高于對照組,而板橋黨參干預組CA3區(qū)Tau蛋白磷酸化程度較模型組減低。5.尼氏染色結果顯示:AD模型組CA1、CA3區(qū)神經元排列紊亂稀少,胞體呈空泡狀,其尼氏小體染色比假手術組明顯變淺,破碎狀且變少,呈溶解狀。板橋黨參干預后神經元從形態(tài)和數(shù)量都有改善,神經元和尼氏小體數(shù)量、形態(tài)均明顯恢復。結論:板橋黨參對AD模型大鼠認知功能障礙具有一定的防治作用,其可能作用機制為降低T216-GSK-3β表達,抑制GSK-3β活性,最終下調Tau蛋白磷酸化水平,同時改善神經元形態(tài)和發(fā)育情況從而增強大鼠空間學習記憶能力。
[Abstract]:Objective: to study whether Banqiao Codonopisis Pilosula Codonopisis can improve cognitive dysfunction in rats with Alzheimer's disease (AD), and to detect the phosphorylation level of Tau protein and its kinase activity in hippocampus of rats. Methods: the AD rats were treated with different doses of BCP decoction to activate the glycogen synthase 3 尾 -glycogen synthase 3 尾 -GSK-3 尾, and the rats were given Morris water maze training on the 9th day. On the 13th day, intragastric injection of phosphatidylinositol 3-kinase specific inhibitor Wortmanninth WT) and protein kinase C-specific inhibitor GF-109203XFGFXX were performed on the 13th day. The water maze test was performed on the 14th day after intragastric administration. The spatial cognitive function of rats in each group was measured. The changes of Tau phosphorylation and protein kinase GSK-3 尾 activity in hippocampus of rats were detected by Western blot and immunohistochemistry. The morphological changes of neurons and the function of neurons in the hippocampus of rats were observed by using Nissl staining method. Results: 1. The results of autonomic behavior test showed that the rats were given the decoction of Panqiao Codonopsis pilosula (Codonopsis pilosula). The number of autonomous activities in the three treatment groups was lower than that in the control group. The water maze test showed that the treatment group could obviously improve the cognitive dysfunction of AD model rats. 3. Western Blot showed that the total GSK-3 尾 of AD model group had no change. However, the activity of T216-GSK-3 尾 was higher than that of sham-operated group, and the expression of p-Tau231 and p-Tau262, p-Tau396and p-Tau404 increased. The phosphorylation level of specific site of Tau protein was significantly down-regulated by Panqiao Codonopsis pilosula. 4. Immunohistochemical method was used to detect the phosphorylation modification of Tau protein in hippocampus tissue. The results showed that the phosphorylation degree of Tau protein in the CA3 region of hippocampus was higher in the control group than that in the control group, while the phosphorylation degree of Tau protein in the CA3 region of the control group was lower than that in the control group. The results of Nissl staining showed that the neurons in CA1 and CA3 region of the control group were poorly arranged. The cell bodies were vacuolated, and their Nissl bodies were obviously shallower, fragmented and less dissolved than those in the sham-operated group. After the intervention of Codonopsis pilosula, the number and morphology of neurons were improved, and the number of neurons and Nissl corpuscles were increased. Conclusion: Codonopsis pilosula has some preventive and therapeutic effects on cognitive dysfunction in AD model rats. The possible mechanism is to decrease the expression of T216-GSK-3 尾, inhibit the activity of GSK-3 尾, and eventually down-regulate the level of phosphorylation of Tau protein. At the same time, the morphology and development of neurons were improved to enhance the spatial learning and memory ability of rats.
【學位授予單位】：湖北民族學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R285.5;R-332

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