【摘要】：目的：miR-101具備APP及COX-2表達(dá)雙重調(diào)節(jié)作用的潛能，為探討miR-101有望成為防治阿爾茨海默病(AD)的新的藥物靶點(diǎn)，我們選用快速老化小鼠（SAMP8）做為研究對(duì)象，，檢測(cè)miR-101、APP和COX在不同月齡的SAMP8鼠海馬組織中的表達(dá)變化狀況。 方法：分別取4、8、12月齡SAMP8和對(duì)抗老化小鼠SAMR1為研究對(duì)象，（1）采用Morris水迷宮實(shí)驗(yàn)測(cè)試SAMP8鼠的空間記憶能力。（2）半定量RT-PCR檢測(cè)SAMP8鼠海馬組織中APP和COX的mRNA表達(dá)變化情況。（3）Western Blot檢測(cè)SAMP8鼠海馬組織中APP和COX的蛋白表達(dá)變化情況。（4）real time PCR檢測(cè)SAMP8鼠海馬組織中miR-101的表達(dá)變化情況。 結(jié)果：（1）Morris水迷宮實(shí)驗(yàn)表明8月齡SAMP8鼠即出現(xiàn)空間記憶障礙，12月齡更為顯著（p0.01），而SAMR1鼠無顯著改變（p0.05）。Aβ42的Western Blot結(jié)果與之一致。（2）半定量RT-PCR結(jié)果顯示SAMP8、SAMR1鼠的海馬組織中APP mRNA僅呈輕微增齡性升高，SAMP8組較SAMR1組稍高，但僅在12月齡組出現(xiàn)顯著差異。（3）Western Blot結(jié)果顯示APP在8月齡SAMP8鼠中升高最顯著（p0.01），12月齡有下降趨勢(shì)，而對(duì)照組SAMR1鼠卻無增齡性顯著改變。（4）real time PCR結(jié)果顯示miR-101在SAMP8鼠中呈顯著增齡性降低。（5）各組小鼠COX-2的mRNA和蛋白水平的變化趨勢(shì)與APP相似，而COX-1的mRNA和蛋白水平均無顯著差異。 結(jié)論：（1）SAMP8鼠早期即可自發(fā)出現(xiàn)空間記憶障礙，并伴有Aβ沉積。（2）SAMP8鼠海馬組織中APP和COX-2的表達(dá)主要受轉(zhuǎn)錄后水平調(diào)控。（3）miR-101可能調(diào)控APP和COX-2的蛋白表達(dá)，而不影響COX-1的表達(dá)。（4）miR-101可能成為防治AD的新的藥物靶點(diǎn)。
[Abstract]:Objective: miR-101 has the potential to regulate the expression of APP and COX-2. In order to explore the potential of miR-101 as a new drug target for the prevention and treatment of (AD) in Alzheimer's disease, we selected the rapidly aging mouse (SAMP8) as the research object. The expression of miR-101,APP and COX in hippocampal tissue of SAMP8 rats of different months of age was detected. Methods: 12-month-old SAMP8 and anti-aging mice SAMR1 were used as the research objects. (1) Morris water maze test was used to test the spatial memory ability of SAMP8 mice. (2) Semi-quantitative RT-PCR was used to detect the changes of mRNA expression of APP and COX in the hippocampus of SAMP8 rats. (3) the expression of APP and COX in the hippocampus of SAMP8 rats was detected by semi-quantitative RT-PCR. The changes of protein expression of APP and COX in hippocampus of SAMP8 rats were detected. (4) the expression of miR-101 in hippocampus of SAMP8 rats was detected by) real time PCR. Results: (1) Morris water maze test showed that 8 months old SAMP8 rats had spatial memory impairment, especially at 12 months old (p0.01), while SAMR1 mice had no significant change (p0.05). A 尾 42 Western Blot results were consistent with the results of Western Blot). (2) Semi-quantitative RT-PCR results showed APP mRNA in the hippocampus of SAMP8,SAMR1 rats. There was only a slight increase in age, and the SAMP8 group was slightly higher than the SAMR1 group. But there was significant difference only in the 12 month old group. (3) Western Blot results showed that APP increased most significantly in 8 months old SAMP8 mice (p0. 01), and decreased at 12 months old. The results of 4) real time PCR showed that miR-101 decreased significantly in SAMP8 mice. (5) the change trend of mRNA and protein levels of COX-2 in each group was similar to that of APP, but there was no significant difference in mRNA and protein levels in COX-1. Conclusion: (1) the spatial memory disorder and A 尾 deposition can occur spontaneously in SAMP8 rats at early stage. (2) the expression of APP and COX-2 in hippocampus of SAMP8 rats is mainly regulated by posttranscriptional level. (3) miR-101 may regulate the expression of APP and COX-2 protein. (4) miR-101 may be a new drug target for the prevention and treatment of AD.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R749.16

【參考文獻(xiàn)】

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1 高林;陳烈冉;賈延R

本文編號(hào)：2278476