本文關(guān)鍵詞： 代謝性谷氨酸受體 β-淀粉樣蛋白 阿爾茨海默病 LTD Caspase　出處：《寧波大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：研究mGlu受體在阿爾茨海默病早期病理機(jī)制中的作用，并探討Aβ介導(dǎo)的突觸可塑性調(diào)制中的神經(jīng)元內(nèi)Caspase、p38MAPK、TACE、mTOR等信號(hào)通路的作用，為發(fā)現(xiàn)新型的藥物靶點(diǎn)、治療阿爾茨海默病提供理論和實(shí)驗(yàn)依據(jù)。 方法：所有實(shí)驗(yàn)均在橫切腦片的海馬齒狀回或CA1區(qū)進(jìn)行。用3周齡wistar雄性大鼠快速斷頭后制成350微米腦片，并置于含有95%氧氣飽和的人工腦脊液的孵育槽內(nèi)，，室溫下孵育一小時(shí)，然后將腦片轉(zhuǎn)移到記錄槽中，在海馬齒狀回或CA1區(qū)，使用標(biāo)準(zhǔn)電生理技術(shù)記錄場興奮性突觸后電位和LTD。記錄的fEPSP峰值用pClamp軟件分析，用基礎(chǔ)水平的相對(duì)百分?jǐn)?shù)形式表示LTD的幅度。LTD值以均數(shù)±標(biāo)準(zhǔn)誤(means±S.E.M.)表示，并進(jìn)行雙尾t檢驗(yàn)和單因素方差分析（ANOVA）。 結(jié)果：在海馬齒狀回和CA1區(qū)，強(qiáng)LFS刺激能誘導(dǎo)產(chǎn)生LTD，弱LFS則不能，但在可溶性Aβ寡聚體的參與下，弱LFS可誘導(dǎo)出穩(wěn)定的LTD。NMDAR特異性拮抗劑D-AP5不能阻斷這種Aβ介導(dǎo)的LTD增強(qiáng)，而相反的，mGluR受體拮抗劑LY341495可阻斷這種LTD。另外caspase抑制劑、p38MAPK抑制劑SB203580、PTP抑制劑氧化苯胂、均能逆轉(zhuǎn)Aβ介導(dǎo)的LTD增強(qiáng)，而mTOR抑制劑Rapamycin和TACE抑制劑TAPI-2沒有明顯作用。 結(jié)論：可溶性Aβ寡聚體能增強(qiáng)弱LFS誘導(dǎo)的LTD，且這種增強(qiáng)作用是由mGluR參與的，而NMDAR不參與Aβ對(duì)LTD的增強(qiáng)。Aβ對(duì)LTD的增強(qiáng)作用可能涉及神經(jīng)元內(nèi)Caspase、p38、PTP等信號(hào)通路的參與。提示這些信號(hào)通路的胞內(nèi)激酶可能是治療阿爾茨海默病的潛在靶點(diǎn)。
[Abstract]:Aim: to study the role of mGlu receptor in the early pathological mechanism of Alzheimer's disease, and to explore the role of Caspasep38MAPKnTOR and other signaling pathways in synaptic plasticity modulation mediated by A 尾 in order to find new drug targets. To provide theoretical and experimental evidence for the treatment of Alzheimer's disease. Methods: all the experiments were carried out in the dentate gyrus or CA1 region of the transected brain slices. Three week-old male wistar rats were quickly decapitated into 350micron brain slices and placed in incubators with artificial cerebrospinal fluid (CSF) containing 95% oxygen saturation. After incubating at room temperature for one hour, the brain slices were transferred to the recording trough, and the excitatory postsynaptic potential and the peak value of fEPSP recorded in the dentate gyrus or CA1 region were recorded using standard electrophysiological techniques. The recorded peak values of fEPSP were analyzed by pClamp software. The amplitude of LTD was expressed by the relative percentage of basic level. The value of LTD was expressed as mean 鹵standard error means 鹵S.E.M., and double tail t test and single factor ANOVAA analysis were performed. Results: in hippocampal dentate gyrus and CA1 region, strong LFS stimulation could induce LTD, while weak LFS could not, but weak LFS could induce stable LTD.NMDAR specific antagonist D-AP5 to block the A 尾 -mediated LTD enhancement, with the participation of soluble A 尾 oligomer. On the other hand, caspase inhibitor, SB203580 PTP inhibitor, could reverse the A 尾 -mediated LTD enhancement, but mTOR inhibitor Rapamycin and TACE inhibitor TAPI-2 had no obvious effect. Conclusion: soluble A 尾 oligomerization can enhance LTD induced by weak LFS, and this enhancement is mediated by mGluR. NMDAR does not participate in the enhancement of LTD by A 尾. The enhancement of LTD by A 尾 may involve the involvement of signal pathways such as Caspase p38 PTP in neurons, suggesting that the intracellular kinase of these signaling pathways may be a potential target for the treatment of Alzheimer's disease.
【學(xué)位授予單位】：寧波大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R749.16

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 武美娜;祁金順;喬健天;;β-淀粉樣蛋白抑制海馬長時(shí)程增強(qiáng)機(jī)制的研究進(jìn)展[J];生理科學(xué)進(jìn)展;2006年03期

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