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大鼠急性一氧化碳中毒后遲發(fā)性腦病模型的建立
作者：趙天智，常耀明，李金聲，謝小萍【關(guān)鍵詞】 Morris水迷宮；一氧化碳中毒；遲發(fā)性腦病；大鼠
Establishment of delayed neuropsychologic sequelae rat model after acute carbon monoxide poisoning
【Abstract】 AIM: To establish the delayed neuropsychologic sequelae rat model after acute carbon monoxide (CO) poisoning for further elucidating its pathogenesis. METHODS: Male SD rats (240-280 g BW) were poisoned with CO in the animal experimental hyperbaric oxygen chamber. Cognitive ability was measured by the escape latency of searching the objective in the Morris water maze. The brains of the rats (3, 7, 10, 20 d after poisoning) were taken for paraffin pathological section and HE staining to observe the pathological change in cerebral cortex and hippocampal area. RESULTS: Rats lost consciousness when they were exposed to 2000 ppm (part per million) CO for 40 min and then 3000 ppm for up to 20 min. Maze test showed that the escape latency of the CO poisoned rats was significantly longer than the air exposed rats (F=4.74，P=0.047). The pathological examination revealed apparent neuronal degeneration and necrosis in the cerebral cortex and hippocampal area in CO poisoned rats. CONCLUSION: Besides the evidence of pathologic results, our models basically simulate the praxiologic change induced by central nervous system damage in the patients with delayed neuropsychologic sequelae after CO poisoning.
【Keywords】 Morris water maze; carbon monoxide poisoning; delayed neuropsychologic sequelae; rats
【摘要】 目的: 建立大鼠急性一氧化碳（CO）中毒致遲發(fā)性腦病模型，以探討其發(fā)病機(jī)制. 方法: 質(zhì)量240~280 g雄性SD大鼠，于動物實(shí)驗(yàn)高壓氧艙內(nèi)行急性CO暴露，以Morris水迷宮中搜索目標(biāo)的逃避潛伏期(escape latency)來評價大鼠的認(rèn)知記憶能力，并于染毒后3，7，10，20 d取腦組織，常規(guī)制備石蠟病理切片，行HE染色觀察急性CO中毒后大鼠腦皮質(zhì)及海馬神經(jīng)元的病理性改變. 結(jié)果:大鼠在2000×10-6體積分?jǐn)?shù)CO濃度和3000×10-6體積分?jǐn)?shù)CO濃度下分別暴露40 min和20 min后全部昏迷，Morris水迷宮測試發(fā)現(xiàn)CO暴露組大鼠逃避潛伏期顯著落后于空氣對照組（F=4.74，P=0.047），病理學(xué)檢查發(fā)現(xiàn)CO暴露組大鼠的皮質(zhì)及海馬有明顯的神經(jīng)元變性壞死. 結(jié)論: 本實(shí)驗(yàn)建立的模型基本模擬了CO中毒后遲發(fā)性腦病患者中樞神經(jīng)系統(tǒng)損傷的行為學(xué)特征改變，且有相應(yīng)的病理學(xué)檢測結(jié)果作為其佐證.
【關(guān)鍵詞】 Morris水迷宮；一氧化碳中毒；遲發(fā)性腦�。淮笫�
【中圖號】 R595.1
0引言
一氧化碳（carbon monoxide, CO）中毒后3%~30%的患者經(jīng)過一段時間的“假愈期”會出現(xiàn)以癡呆、精神癥狀和錐體外系癥狀為主遲發(fā)性腦病(delayed neuropsychologic sequelae, DNS)［1］. 目前其發(fā)病機(jī)制仍未完全闡明，缺少可靠的動物模型是阻礙其深入研究的重要原因之一［2］，主要問題在于中毒濃度的掌握和動物行為學(xué)評價方法的缺陷上. 因此，我們嘗試采用急性靜態(tài)CO吸入的方法制備大鼠的DNS動物模型，并采用Morris水迷宮來評價中毒后大鼠認(rèn)知記憶能力的改變，為進(jìn)一步研究DNS的發(fā)病機(jī)制提供客觀有效的手段.
1材料和方法
1.1材料
1.1.1CO氣體于染毒前新鮮制備.
1.1.2染毒裝置DWC4501150型（上海七零一所）動物實(shí)驗(yàn)高壓氧艙，艙體為直徑0.45 m，長1 m的圓筒形，有效空間160 L，可同時對4只大鼠染毒.
1.1.3行為實(shí)驗(yàn)裝置由Morris水迷宮和圖像自動監(jiān)視系統(tǒng)(Morris Maze Experimental Assistant System, MMEAS)組成（第四軍醫(yī)大學(xué)防原教研室提供）. Mor
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