麻醉手术对不同性别阿尔兹海默病转基因小鼠的认知功能的影响

发布时间：2018-01-20 02:34

本文关键词： 阿尔兹海默病手术七氟烷认知功能突触标志蛋白和亲环素D　出处：《吉林大学》2017年博士论文　论文类型：学位论文

【摘要】：目的:麻醉被认为是术后认知功能障碍的一个潜在的诱发因素,同时,认知功能下降是阿尔兹海默病的一个标志,因此,有假说认为全身麻醉与阿尔兹海默病有着或多或少的关联。研究结果各有不同,目前的发现还没有定论能证明全身麻醉药物会在阿尔兹海默病的动物模型中引起术后认知功能障碍。麻醉本身或麻醉手术都可能会通过加快其神经病发病机理而促进阿尔兹海默病(AD)发病进程。还有一些研究支持不同的研究结果。然而,性别差异在这些研究中并未被充分考虑,而且,目前关于是男性还是女性阿尔兹海默病患者更容易患有术后认知功能障碍还不清楚。因此,本研究决定设计一个有说服力的实验来研究说明是否麻醉手术对于雌性和雄性阿尔兹海默病转基因小鼠以及在雌性亲环素D(Cyp D)基因敲除的阿尔兹海默病转基因小鼠中有不同的作用。方法:本研究应用雄性和雌性阿尔兹海默病转基因小鼠以及雌性Cyp D基因敲除的阿尔兹海默病转基因小鼠,对照组小鼠置于60%氧气环境中2小时,处理组小鼠接受3%七氟烷和60%氧气复合气体全身麻醉下的腹部手术(麻醉手术)。本实验用条件恐惧实验(FCS)来测评小鼠的认知功能。我们选取两种海马水平的标志蛋白,突触后致密物95(PSD-95)和突触素(SVP),来用Western blot分析法检测这两种蛋白量。结果:本研究发现麻醉手术在雌性阿尔兹海默病转基因小鼠中会导致在麻醉术后第七天条件恐惧实验的环境测试中的不动状态时间显著减少(P=0.0159),而雄性阿尔兹海默病转基因鼠在麻醉术后第七天条件恐惧实验的环境测试中不动状态时间并没有显著减少(P=0.4988)。麻醉手术导致术后第七天在雌性阿尔兹海默病转基因小鼠中海马组织内的突触后致密物95(P=0.0071)和突触素(P=0.0061)两种突触标志蛋白水平均显著降低,而在雄性阿尔兹海默病转基因小鼠中,麻醉术后第七天,小鼠中海马组织内的突触后致密物95(P=0.9973)和突触素(P=0.2670)两种突触标志蛋白水平并没有显著降低。进一步研究发现,雌性亲环素D基因敲除的阿尔兹海默病转基因小鼠在麻醉术后第七天条件恐惧实验的环境测试中不动状态时间也没有显著减少(P=0.1974)。而麻醉手术后第七天,在雌性亲环素D基因敲除的阿尔兹海默病转基因小鼠中海马组织内的突触后致密物95(PSD-95)(P=0.1126)和突触素(SVP)(P=0.3654)水平也没有显著降低。结论:这些实验数据说明麻醉手术会在阿尔兹海默病转基因小鼠中导致性别相关的认知功能损害,和性别相关的海马内突触标志蛋白水平的降低,而这内在的机制很可能是与线粒体有关的。这些研究发现可以促进临床研究来进一步研究发现是否女性阿尔兹海默病患者相比于男性阿尔兹海默病患者更易患有术后认知功能障碍。
[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.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R749.16

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