發(fā)布時(shí)間：2018-03-01 02:33

  本文關(guān)鍵詞： 阿爾茨海默病 小檗堿 IGF-1 IGF-1R　出處：《中南大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：背景：中樞胰島素抵抗與阿爾茨海默病密切相關(guān)。IGF-1在胰島素抵抗中扮演重要作用,在AD模型鼠上增加IGF-1的表達(dá),可以使Aβ沉積和tau蛋白磷酸化減少。研究表明小檗堿可提高IGF-1的表達(dá),改善糖尿病鼠的認(rèn)知功能。但目前小檗堿與AD模型鼠病理生理和認(rèn)知功能的關(guān)系,國(guó)內(nèi)外尚無文獻(xiàn)報(bào)道。 目的：建立具有中樞胰島素抵抗的阿爾茨海默病大鼠模型,初步探討小檗堿對(duì)阿爾茨海默病模型大鼠認(rèn)知功能的改善及其可能的作用機(jī)制。 方法：清潔級(jí)成年雄性SD大鼠經(jīng)篩選后隨機(jī)分為正常組、假手術(shù)組、模型組和干預(yù)組。采用雙側(cè)側(cè)腦室注射鏈脲佐菌素建立阿爾茨海默病模型。采用Morris水迷宮檢測(cè)大鼠的記憶認(rèn)知功能；剛果紅染色觀察海馬部位是否存在β-淀粉樣蛋白沉積；HE染色、Nissl染色觀察海馬組織形態(tài)學(xué)的變化；免疫組織化學(xué)法觀察海馬CA3區(qū)IGF-1及IGF-1R表達(dá)的影響。 結(jié)果： 1、正常組和假手術(shù)組比較：病理組織形態(tài)學(xué)改變不明顯；IGF-1和IGF-1R的陽(yáng)性表達(dá)細(xì)胞數(shù)無統(tǒng)計(jì)學(xué)差異(P0.05)。 2、AD模型組與正常組比較：剛果紅染色可見橘紅色斑塊狀物質(zhì),提示為Ap蛋白沉積；海馬CA3區(qū)錐體細(xì)胞排列稀疏、紊亂,錐體細(xì)胞數(shù)目明顯減少(P0.05)；海馬CA3區(qū)IGF-1和IGF-1R陽(yáng)性表達(dá)細(xì)胞數(shù)目減少(P0.05)；大鼠逃避潛伏期明顯延長(zhǎng)(P0.05),平均穿越平臺(tái)次數(shù)減少(P0.05)。 3、小檗堿干預(yù)組與AD模型組比較：剛果紅染色可見橘紅色斑塊狀物質(zhì)明顯減少,海馬CA3區(qū)錐體細(xì)胞排列緊湊、紊亂程度減輕,錐體細(xì)胞數(shù)目增多(P0.05)；海馬CA3區(qū)IGF-1和IGF-1R陽(yáng)性表達(dá)細(xì)胞數(shù)目增多(P0.05)；大鼠逃避潛伏期明顯縮短(P0.05),平均穿越平臺(tái)次數(shù)增多(P0.05)。 結(jié)論： 1、經(jīng)側(cè)腦室內(nèi)注射鏈脲佐菌素可成功地建立具有中樞胰島素抵抗的阿爾茨海默病大鼠模型。 2、小檗堿通過增加大鼠海馬CA3區(qū)IGF-1和IGF-1R蛋白的表達(dá),減少Aβ蛋白沉積、減輕神經(jīng)元丟失、改善錐體細(xì)胞形態(tài),提高AD模型大鼠的認(rèn)知功能。
[Abstract]:Background: central insulin resistance is closely related to Alzheimer's disease. IGF-1 plays an important role in insulin resistance and increases the expression of IGF-1 in AD mice. Berberine can increase the expression of IGF-1 and improve the cognitive function of diabetic rats. However, the relationship between berberine and pathophysiology and cognitive function of AD model rats has not been reported. Aim: to establish a rat model of Alzheimer's disease with central insulin resistance and to explore the improvement of cognitive function and the possible mechanism of berberine on Alzheimer's disease model. Methods: adult male SD rats of clean grade were randomly divided into normal group and sham operation group after screening. Model group and intervention group. The model of Alzheimer's disease was established by bilateral intracerebroventricular injection of streptozotocin. The memory and cognitive function of rats was measured by Morris water maze. Congo red staining was used to observe the presence of 尾 -amyloid deposition in hippocampus. The morphological changes of hippocampal tissue were observed by HE staining, and the expression of IGF-1 and IGF-1R in hippocampal CA3 were observed by immunohistochemical method. Results:. 1. Comparison between normal group and sham operation group: there was no significant difference in the number of IGF-1 and IGF-1R positive cells between normal group and sham operation group (P 0.05). 2Compared with normal group, Congo red staining showed orange plaques, suggesting that AP protein was deposited, pyramidal cells in hippocampal CA3 were sparse and disordered. The number of pyramidal cells was significantly decreased, the number of IGF-1 and IGF-1R positive expression cells in hippocampal CA3 region was decreased, and the escape latency of rats was significantly prolonged (P 0.05), and the average number of times of crossing the platform was decreased (P 0.05). 3Compared with AD model group, Congo red staining showed that orange plaques were decreased, pyramidal cells in hippocampal CA3 were compact, and the degree of disorder was reduced. The number of pyramidal cells increased, the number of IGF-1 and IGF-1R positive cells increased in CA3 area of hippocampus, and the escape latency of rats shortened P0.05, and the average number of crossing platform increased. Conclusion:. 1. Streptozotocin (STZ) injection via lateral ventricle can successfully establish the model of Alzheimer's disease with central insulin resistance. 2. Berberine can increase the expression of IGF-1 and IGF-1R in CA3 area of rat hippocampus, reduce the deposition of A 尾 protein, reduce the loss of neurons, improve the morphology of pyramidal cells and enhance the cognitive function of AD rats.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R749.16

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