【摘要】：目的:術(shù)前使用右美托咪定對(duì)行體外循環(huán)手術(shù)的老齡大鼠術(shù)后認(rèn)知功能的影響及可能機(jī)制的探討。方法:18~20月齡健康雄性SD大鼠90只,隨機(jī)分為實(shí)驗(yàn)組、對(duì)照組和右美組,每組30只,實(shí)驗(yàn)組大鼠腹腔注射生理鹽水后進(jìn)行體外循環(huán)手術(shù),對(duì)照組大鼠不進(jìn)行任何處理,右美組大鼠腹腔注射50ug/kg右美托咪定后進(jìn)行體外循環(huán)手術(shù)。選擇Morris水迷宮檢測(cè)三組大鼠空間學(xué)習(xí)和記憶能力,選擇穿梭箱實(shí)驗(yàn)檢測(cè)三組大鼠學(xué)習(xí)條件反射的能力,選擇曠場(chǎng)實(shí)驗(yàn)檢測(cè)三組大鼠在新異環(huán)境中的適應(yīng)能力和認(rèn)知能力。采用Elisa法測(cè)定腦脊液中Aβ、p-Tau及PSD95蛋白含量;采用免疫組化法測(cè)定海馬及前額葉皮質(zhì)腦組織中Aβ、p-Tau及PSD95蛋白含量。結(jié)果:共有51只大鼠完成本實(shí)驗(yàn)全過程,其中實(shí)驗(yàn)組23只,右美組28只,對(duì)照組30只,三組大鼠實(shí)驗(yàn)完成率(分別為76.7%,93.3%和100%)組間差異無統(tǒng)計(jì)學(xué)意義(P0.05)。1.Morris水迷宮實(shí)驗(yàn):(1)定位航行實(shí)驗(yàn)三組大鼠術(shù)前逃避潛伏期無明顯差異(P0.05),術(shù)后第31~35天各組大鼠逃避潛伏期,與實(shí)驗(yàn)組相比,對(duì)照組與右美組大鼠逃避潛伏期較短(P0.05);與對(duì)照組相比,右美組大鼠術(shù)后第31、32、34、35天逃避潛伏期較長(P0.05)。(2)空間探索實(shí)驗(yàn)與實(shí)驗(yàn)組相比,對(duì)照組與右美組大鼠穿越原平臺(tái)次數(shù)較多(P0.05);與對(duì)照組相比,右美組大鼠穿越原平臺(tái)次數(shù)較少(P0.05)。2.穿梭箱實(shí)驗(yàn)與實(shí)驗(yàn)組相比,對(duì)照組與右美組大鼠主動(dòng)回避反應(yīng)次數(shù)較多(P0.05),主動(dòng)及被動(dòng)回避反應(yīng)潛伏期較短(P0.05);與對(duì)照組相比,右美組大鼠主動(dòng)回避反應(yīng)次數(shù)較少(P0.01)。3.曠場(chǎng)實(shí)驗(yàn)與實(shí)驗(yàn)組相比,對(duì)照組與右美組大鼠直立次數(shù)較多(P0.05),中央格停留時(shí)間較短(P0.05);與對(duì)照組相比,右美組大鼠中央格停留時(shí)間較長(P0.05)。4.腦脊液蛋白含量測(cè)試結(jié)果與實(shí)驗(yàn)組相比,對(duì)照組和右美組大鼠腦脊液Aβ及PSD95蛋白含量較高(P0.05),p-Tau蛋白含量較低(P0.05);與對(duì)照組相比,右美組大鼠腦脊液Aβ蛋白含量較低(P0.05)。5.腦組織蛋白陽性神經(jīng)元個(gè)數(shù)的比較與實(shí)驗(yàn)組相比,對(duì)照組和右美組大鼠海馬及前額葉皮質(zhì)腦組織Aβ、p-Tau蛋白陽性神經(jīng)元個(gè)數(shù)減少,PSD95蛋白陽性神經(jīng)元個(gè)數(shù)增加(P0.05);與對(duì)照組相比,右美組海馬腦組織Aβ蛋白陽性神經(jīng)元個(gè)數(shù)增加(P0.05),PSD95蛋白陽性神經(jīng)元個(gè)數(shù)減少(P0.05),右美組前額葉皮質(zhì)腦組織Aβ、p-Tau蛋白陽性神經(jīng)元個(gè)數(shù)增加(P0.05),PSD95蛋白陽性神經(jīng)元個(gè)數(shù)減少(P0.05)。結(jié)論:1老齡大鼠行體外循環(huán)手術(shù)對(duì)術(shù)后認(rèn)知功能的影響在行為學(xué)方面表現(xiàn)為:影響空間學(xué)習(xí)和記憶的形成,導(dǎo)致學(xué)習(xí)條件反射的能力降低,并減弱其在新異環(huán)境中的適應(yīng)能力和認(rèn)知能力;而術(shù)前使用右美托咪定能使上述癥狀得到改善。2行體外循環(huán)手術(shù)的老齡大鼠腦脊液中Aβ及PSD95蛋白含量增高,p-Tau蛋白含量降低;而術(shù)前使用右美托咪定能降低腦脊液中蛋白含量改變的幅度。3行體外循環(huán)手術(shù)的老齡大鼠海馬及前額葉皮質(zhì)腦組織中Aβ、p-Tau蛋白呈低表達(dá),PSD95蛋白呈高表達(dá);而術(shù)前使用右美托咪定能降低目標(biāo)區(qū)域腦組織中目標(biāo)蛋白表達(dá)異常的程度。4術(shù)前使用右美托咪定能夠降低行體外循環(huán)手術(shù)的老齡大鼠術(shù)后認(rèn)知功能障礙的發(fā)生,其機(jī)制可能是通過調(diào)節(jié)Aβ、p-Tau及PSD95蛋白表達(dá)來實(shí)現(xiàn)的。
[Abstract]:Objective: To investigate the effect and possible mechanism of postoperative cognitive function of the aged rats undergoing cardiopulmonary bypass operation before and after the operation. Methods: 90 healthy male SD rats from 18 to 20 months of age were randomly divided into experimental group, control group and right group. In the right group, the rats were injected with 50ug/ kg dexmetomidine, and the operation was carried out after cardiopulmonary bypass. The spatial learning and memory ability of three groups of rats were tested by the Morris water maze. The ability of three groups of rats to study the conditioned reflex was selected by the experiment of the shuttle box, and the adaptive ability and the cognitive ability of the three groups of rats in the new environment were selected. The content of A-, p-Tau and PSD95 in the cerebrospinal fluid was determined by elisa, and the content of A-, p-Tau and PSD95 in the brain of the hippocampus and prefrontal cortex was determined by immunohistochemistry. Results: The whole process of the experiment was completed in 51 rats, 23 of the experimental group, 28 in the right and 30 in the control group, and the experimental completion rate of the three groups (76.7%, 93.3% and 100%, respectively). (1) There was no significant difference in the avoidance latency of the three groups of rats (P0.05). The latency of the 31, 32, 34 and 35 days after operation in the right group was longer than that in the right group (P0.05). (2) Compared with the experimental group, the number of the rats in the control group and the right group was much higher than that of the control group (P0.05); the number of the rats in the right and the right group was less than that of the control group (P0.05). Compared with the experimental group, the number of active avoidance responses in the control group and the right group (P0.05), the active and passive avoidance response latency was shorter (P <0.05), and the number of active avoidance responses in the right-group rats was less than that of the control group (P0.01). Compared with the experimental group, the vertical number of the rats in the control group and the right group was much higher (P0.05), and the residence time of the central cell was shorter (P <0.05), and the residence time of the central cell in the right-US group was longer than that of the control group (P0.05). Compared with the control group, the content of CSF-A and PSD95 in the spinal fluid of the control group and the right group were higher (P0.05), and the content of the P-Tau protein was lower (P0.05). Compared with the control group, the number of positive neurons in the brain tissue of the rats in the control group and the right group decreased, the number of the positive neurons of the p-Tau protein was decreased, and the number of the positive neurons of the PSD95 protein was increased (P0.05); and compared with the control group, the number of the positive neurons of the brain tissue protein was reduced, and the number of the positive neurons of the PSD95 protein was increased (P0.05). The number of positive neurons in the hippocampus of the right group was increased (P0.05), the number of positive neurons of the PSD95 protein was decreased (P0.05), and the number of positive neurons in the prefrontal cortex of the right group was increased (P0.05), and the number of positive neurons of the PSD95 protein was decreased (P0.05). Conclusion: 1. The effect of cardiopulmonary bypass on the cognitive function of aged rats is shown as follows: the formation of spatial learning and memory, the ability of learning conditioned reflex, and the ability to adapt to the cognitive function in the new environment; The results showed that the content of A-and PSD95 in the cerebrospinal fluid of aged rats with cardiopulmonary bypass (CPB) increased, and the content of p-Tau protein was lower. The changes of protein content in the CSF can be reduced by the use of the right meetomidate before the operation. The expression of A-and p-Tau in the brain of the hippocampus and the prefrontal cortex of the aged rats with cardiopulmonary bypass is low, and the PSD95 protein is highly expressed. It is possible to reduce the level of target protein expression in the brain tissue of the target region by using the right-meetomidate before operation. p-Tau and pSD95 protein expression.
【學(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R614

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