發(fā)布時間：2018-01-20 02:34

  本文關(guān)鍵詞： 阿爾茲海默病 手術(shù) 七氟烷 認知功能 突觸標志蛋白 和親環(huán)素D　出處：《吉林大學(xué)》2017年博士論文　論文類型：學(xué)位論文

【摘要】：目的:麻醉被認為是術(shù)后認知功能障礙的一個潛在的誘發(fā)因素,同時,認知功能下降是阿爾茲海默病的一個標志,因此,有假說認為全身麻醉與阿爾茲海默病有著或多或少的關(guān)聯(lián)。研究結(jié)果各有不同,目前的發(fā)現(xiàn)還沒有定論能證明全身麻醉藥物會在阿爾茲海默病的動物模型中引起術(shù)后認知功能障礙。麻醉本身或麻醉手術(shù)都可能會通過加快其神經(jīng)病發(fā)病機理而促進阿爾茲海默病(AD)發(fā)病進程。還有一些研究支持不同的研究結(jié)果。然而,性別差異在這些研究中并未被充分考慮,而且,目前關(guān)于是男性還是女性阿爾茲海默病患者更容易患有術(shù)后認知功能障礙還不清楚。因此,本研究決定設(shè)計一個有說服力的實驗來研究說明是否麻醉手術(shù)對于雌性和雄性阿爾茲海默病轉(zhuǎn)基因小鼠以及在雌性親環(huán)素D(Cyp D)基因敲除的阿爾茲海默病轉(zhuǎn)基因小鼠中有不同的作用。方法:本研究應(yīng)用雄性和雌性阿爾茲海默病轉(zhuǎn)基因小鼠以及雌性Cyp D基因敲除的阿爾茲海默病轉(zhuǎn)基因小鼠,對照組小鼠置于60%氧氣環(huán)境中2小時,處理組小鼠接受3%七氟烷和60%氧氣復(fù)合氣體全身麻醉下的腹部手術(shù)(麻醉手術(shù))。本實驗用條件恐懼實驗(FCS)來測評小鼠的認知功能。我們選取兩種海馬水平的標志蛋白,突觸后致密物95(PSD-95)和突觸素(SVP),來用Western blot分析法檢測這兩種蛋白量。結(jié)果:本研究發(fā)現(xiàn)麻醉手術(shù)在雌性阿爾茲海默病轉(zhuǎn)基因小鼠中會導(dǎo)致在麻醉術(shù)后第七天條件恐懼實驗的環(huán)境測試中的不動狀態(tài)時間顯著減少(P=0.0159),而雄性阿爾茲海默病轉(zhuǎn)基因鼠在麻醉術(shù)后第七天條件恐懼實驗的環(huán)境測試中不動狀態(tài)時間并沒有顯著減少(P=0.4988)。麻醉手術(shù)導(dǎo)致術(shù)后第七天在雌性阿爾茲海默病轉(zhuǎn)基因小鼠中海馬組織內(nèi)的突觸后致密物95(P=0.0071)和突觸素(P=0.0061)兩種突觸標志蛋白水平均顯著降低,而在雄性阿爾茲海默病轉(zhuǎn)基因小鼠中,麻醉術(shù)后第七天,小鼠中海馬組織內(nèi)的突觸后致密物95(P=0.9973)和突觸素(P=0.2670)兩種突觸標志蛋白水平并沒有顯著降低。進一步研究發(fā)現(xiàn),雌性親環(huán)素D基因敲除的阿爾茲海默病轉(zhuǎn)基因小鼠在麻醉術(shù)后第七天條件恐懼實驗的環(huán)境測試中不動狀態(tài)時間也沒有顯著減少(P=0.1974)。而麻醉手術(shù)后第七天,在雌性親環(huán)素D基因敲除的阿爾茲海默病轉(zhuǎn)基因小鼠中海馬組織內(nèi)的突觸后致密物95(PSD-95)(P=0.1126)和突觸素(SVP)(P=0.3654)水平也沒有顯著降低。結(jié)論:這些實驗數(shù)據(jù)說明麻醉手術(shù)會在阿爾茲海默病轉(zhuǎn)基因小鼠中導(dǎo)致性別相關(guān)的認知功能損害,和性別相關(guān)的海馬內(nèi)突觸標志蛋白水平的降低,而這內(nèi)在的機制很可能是與線粒體有關(guān)的。這些研究發(fā)現(xiàn)可以促進臨床研究來進一步研究發(fā)現(xiàn)是否女性阿爾茲海默病患者相比于男性阿爾茲海默病患者更易患有術(shù)后認知功能障礙。
[Abstract]:Objective: anesthesia is considered to be a potential predisposing factor for postoperative cognitive dysfunction, and cognitive impairment is a marker of Alzheimer's disease. There are hypotheses that general anesthesia is more or less associated with Alzheimer's disease. There is no conclusive evidence that general anaesthetic drugs cause postoperative cognitive impairment in Alzheimer's disease models. Anesthesia itself or surgery may accelerate the pathogenesis of neuropathy. Promoting Alzheimer's disease (. Other studies support different findings. However. Gender differences have not been fully taken into account in these studies, and it is not clear whether men or women with Alzheimer's disease are more likely to suffer from postoperative cognitive impairment. This study decided to design a persuasive experiment to study whether anesthetic surgery is effective in both female and male transgenic mice with Alzheimer's disease and in female cyclophile DCyp D). The effects of gene knockout on Alzheimer's disease transgenic mice were different. Methods: in this study, male and female Alzheimer's disease transgenic mice and female Cyp were used. D-gene knockout of Alzheimer's disease transgenic mice. Mice in the control group were exposed to 60% oxygen for 2 hours. Treatment group mice received abdominal surgery under general anesthesia of 3% sevoflurane and 60% oxygen compound gas (anesthesia operation). To test the cognitive function of the mice, we selected two marker proteins at the hippocampal level. PSD-95) and synaptophysin (SVP). To detect the two proteins by Western blot. Results:. This study found that anesthetic surgery in female Alzheimer's disease transgenic mice resulted in a significant reduction in the time of immobility in environmental tests of the conditioned fear test 7th days after anesthesia. P0. 0159). However, male Alzheimer's disease transgenic mice did not significantly reduce the time of immobility in environmental tests of conditioned fear test 7th days after anaesthesia. 7th days after anesthesia, postsynaptic densification 95 (P0. 0071) and synaptophysin (P0. 0061) in the hippocampal tissue of female transgenic mice with Alzheimer's disease were induced by anaesthesia. The levels of the two synaptic markers were significantly decreased. In male transgenic mice with Alzheimer's disease, 7th days after anesthesia. There was no significant decrease in the levels of two synaptic markers in hippocampus of mice, the postsynaptic denser 95 (0.9973) and the synaptophysin (0.2670). Further studies showed that the two synaptic markers were not significantly reduced. Female cyclin D knockout transgenic mice with Alzheimer's disease did not significantly reduce the time of immobility in environmental tests of conditioned fear test 7th days after anaesthesia. 7th days after anesthesia. Postsynaptic densites 95 PSD-95 P0. 1 126 in hippocampus of transgenic mice with Alzheimer's disease knockout of the female cyclophile D gene and synaptophysin (SVP) (. Conclusion: these experimental data suggest that anesthesia may lead to gender-related cognitive impairment in genetically modified mice with Alzheimer's disease. Reduction of synaptic marker protein levels in the hippocampus associated with sex. And the underlying mechanism is probably involved in mitochondria. These findings have been instrumental in clinical studies to find out whether women with Alzheimer's disease are more likely to have it than men with Alzheimer's disease. Postoperative cognitive impairment.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R749.16

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