【摘要】：術(shù)后認知功能障礙(POCD, Postoperative cognitive dysfunction)是在臨床工作中常見的并發(fā)癥之一,尤其好發(fā)于老年患者麻醉手術(shù)之后。在圍手術(shù)期,患者不僅接受了外科手術(shù)所帶來的軀體創(chuàng)傷,而且承受著一定程度的心理負擔。實驗室研究表明,單純外科手術(shù)可導致動物的認知功能損傷。然而,老年患者圍術(shù)期心理應激是否會對其術(shù)后的學習記憶功能產(chǎn)生影響尚未見報道。本研究擬評估手術(shù)應激及心理應激對老年C57小鼠學習及記憶功能的影響,并進一步探討影響產(chǎn)生的可能機制。第一部分手術(shù)應激與心理應激對老年小鼠學習記憶功能的影響目的：探討手術(shù)應激、心理應激以及心理應激聯(lián)合手術(shù)應激對老年C57小鼠學習及記憶功能的影響。方法：老年雌性C57BL/6小鼠(14月齡,96只),按體重依次排序,隨機分為三個大組：手術(shù)應激組(n=32)、心理應激組(n=32)、聯(lián)合應激組(n=32)；每個大組下設(shè)兩個亞組分別為：干預組(n=16)和對照組(n=16)。手術(shù)應激干預組小鼠接受局麻開腹探查術(shù),其對照組僅接受局麻,不開腹。心理應激干預組小鼠旁觀其他小鼠被電擊15天,每天2次,其對照組小鼠觀察的小鼠未被電擊。聯(lián)合應激干預組在旁觀其他小鼠電擊15天后接受局麻開腹手術(shù),其對照組聯(lián)合上述兩種對照方式。在造模結(jié)束后1-7天,進行曠場實驗、新物體識別實驗和Morris水迷宮實驗評價老年小鼠的學習及記憶功能。結(jié)果：1.手術(shù)應激組和聯(lián)合應激組中的干預組相比其各自對照組的水迷宮逃避潛伏期明顯延長,新物體辨別能力下降；2.心理應激組內(nèi)干預組與對照組的水迷宮逃避潛伏期及新物體辨別能力無明顯差異；3.手術(shù)應激組中干預組與聯(lián)合應激組中干預組的水迷宮逃避潛伏期及新物體辨別能力無明顯差別。結(jié)論：本研究未發(fā)現(xiàn)旁觀電擊實驗所致的心理應激會對老年小鼠的學習記憶能力產(chǎn)生影響,心理應激聯(lián)合手術(shù)應激所致的認知功能損傷程度與單純手術(shù)應激所致的認知功能損傷程度無明顯差別。第二部分手術(shù)應激與心理應激影響老年小鼠學習記憶功能的相關(guān)機制目的：探討手術(shù)應激、心理應激及心理應激聯(lián)合手術(shù)應激對老年C57小鼠學習及記憶功能產(chǎn)生影響的可能機制。方法：老年雌性C57BL/6小鼠(14月齡,108只),按體重依次排序,隨機分為三個大組：手術(shù)應激組(n=36)、心理應激組(n=36)、聯(lián)合應激組(n=36)；每個大組下設(shè)兩個亞組分別為：干預組(n=18)和對照組(n=18)。手術(shù)應激干預組小鼠接受局麻開腹探查術(shù),其對照組僅接受局麻,不開腹。心理應激干預組小鼠旁觀其他小鼠被電擊15天,每天2次,其對照組小鼠觀察的小鼠未被電擊。聯(lián)合應激干預組在旁觀其他小鼠電擊15天后接受局麻開腹手術(shù),其對照組聯(lián)合上述兩種對照方式。在造模結(jié)束后的第1、3、7天,取血、取腦檢測各組C57小鼠血清、皮層及海馬內(nèi)TNF-α、p-AKT、p-mTOR及p-PKCα蛋白含量及海馬CAl區(qū)尼氏小體數(shù)量。結(jié)果：1.尼氏染色發(fā)現(xiàn)在造模后第7天手術(shù)應激干預組和聯(lián)合應激干預組小鼠海馬CA1區(qū)尼氏體數(shù)目顯著低于其余各實驗亞組；2. ELISA結(jié)果顯示造模后第1天手術(shù)應激組干預組和聯(lián)合應激組干預組相比其各自對照組小鼠,血清內(nèi)TNF-α水平顯著升高；3.造模后第1-3天手術(shù)應激組干預組和聯(lián)合應激組干預組相比其各自對照組小鼠,海馬內(nèi)p-AKT表達被顯著抑制,皮層p-AKT無明顯改變；4.造模后第3天,手術(shù)應激組干預組和聯(lián)合應激組干預組相比其各自對照組小鼠,海馬和皮層內(nèi)p-mTOR表達量降低。5.所有干預組小鼠的皮層與海馬內(nèi)p-PKC a蛋白含量在術(shù)后第1天升高,第3天后恢復正常。結(jié)論：海馬CAl區(qū)尼氏小體數(shù)量減少和腦內(nèi)AKT/mTOR信號通路的異常調(diào)節(jié)與老年C57小鼠造模后學習與記憶能力的改變有關(guān)。
[Abstract]:Postoperative cognitive dysfunction (POCD, Postoperative cognitive dysfunction) is one of the common complications in clinical work, especially after anesthesia in elderly patients. In the perioperative period, patients not only receive physical trauma from surgery, but also bear a certain degree of psychological burden. Laboratory studies have shown that However, the influence of psychological stress on the learning and memory function of the elderly patients has not been reported. This study is to evaluate the effect of surgical stress and psychological stress on the learning and memory function of C57 mice and to further explore the possibility of the effect. The effect of surgical stress and psychological stress on the learning and memory function of aged mice in the first part: To explore the effects of surgical stress, psychological stress and psychological stress on the learning and memory function of the aged C57 mice. Methods: the elderly female C57BL/6 mice (14 month old, 96) were sorted in order by weight and were randomly divided into Three large groups: operation stress group (n=32), psychological stress group (n=32), combined stress group (n=32), two subgroups in each group were divided into intervention group (n=16) and control group (n=16). The mice in the operation stress intervention group received local anesthesia open abdominal exploration, the control group only accepted local anesthesia and not open the abdomen. The mice in the psychological stress intervention group looked on the other mice. After 15 days of electric shock, 2 times a day, the mice in the control group were not subjected to electric shock. The combined stress intervention group received local anesthesia for 15 days after the other mice, and the control group combined the two control methods. After the end of the model, the open field experiment, the new object recognition experiment and the Morris water maze test were used to evaluate the elderly. Results: 1. the escape latency of water maze in the control group and the control group were significantly longer than those in the control group, and the discrimination ability of the new objects decreased, and there was no significant difference in the escape latency of water maze and the ability to distinguish the new objects in the 2. psychological stress group and the control group; 3. hands. There was no significant difference in the escape latency of water maze and the ability to distinguish new objects between the intervention group and the intervention group in the intervention group and the intervention group. Conclusion: the study did not find that the psychological stress caused by the observation of the electric shock could affect the learning and memory ability of the aged mice, and the cognitive impairment caused by the psychological stress combined with the operation stress. There is no significant difference in the degree of cognitive impairment caused by degree and simple operation stress. Second the mechanism of the related mechanisms of psychological stress and psychological stress on the learning and memory function of the aged mice: the possible mechanism of the effects of surgical stress, psychological stress and psychological stress combined with surgical stress on the learning and memory function of the aged C57 rats Methods: the elderly female C57BL/6 mice (14 month old, 108) were sorted in order by weight and were randomly divided into three groups: operation stress group (n=36), psychological stress group (n=36), combined stress group (n=36); two subgroups of each group were divided into intervention group (n= 18) and control group (n=18). Operation stress intervention group received local anesthesia open exploration. In the control group, the other mice in the psychological stress intervention group were subjected to electric shock for 15 days, 2 times a day, and the mice in the control group were not subjected to electric shock. The combined stress intervention group received local anesthesia for 15 days after the other mice, and the control group combined the above two control methods. The serum of C57 mice, TNF- alpha, p-AKT, p-mTOR and p-PKC alpha protein content in cortex and hippocampus and the number of Nissl corpuscles in hippocampal CAl region were measured by taking blood after 1,3,7 days after the bundle. Results: 1. Nissl staining found that the number of Nissl bodies in hippocampal CA1 area of the operation stress intervention group and the combined stress intervention group was significantly lower than the rest seventh days after the model building. The results of 2. ELISA showed that the level of TNF- alpha in the serum of the intervention group and the control group was significantly higher than that of the control group of the intervention group and the intervention group of the combined stress group first days after the model building, and the expression of p-AKT in the hippocampus in the hippocampus of the operation stress group and the combined stress group on the 1-3 day after the model building was compared with the control group, and the expression of p-AKT in the hippocampus was observed. There was no significant change in the cortex p-AKT. 4. after third days of the model, the expression of p-mTOR in the hippocampus and the cortex of the intervention group of the operation stress group and the combined stress group decreased in the hippocampus and the cortex of the control group. The content of p-PKC a protein in the cortex and hippocampus of all the mice in the.5. intervention group increased at first days after the operation, and recovered to normal after third days. The decrease of Nissl bodies and abnormal regulation of AKT/mTOR signaling pathway in hippocampal CAl region are related to changes in learning and memory ability in aged C57 mice after modeling.
【學位授予單位】：中國人民解放軍醫(yī)學院
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R614

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